Electrical stimulation of dorsal and ventral striatum differentially alters the copulatory behavior of male rats.

Sexual behavior is a natural reward that activates striatal dopaminergic (DA) circuits, and dopamine exerts a facilitative influence on copulation. Electrical stimulation of the striatum has been shown to be rewarding, but its effect on male sexual behavior display has not been established. The objective of the present work was to assess the effects of low- and high-frequency electrical stimulation of the dorsal and ventral striatum on male rat sexual behavior expression. To this aim, copulatory activity of sexually experienced male rats was recorded during electrical stimulation of the nucleus accumbens (NAcc) or caudate-putamen (CP), at each stimulation frequency, before and after sexual exhaustion. Results showed that electrical stimulation of the NAcc at both frequencies increased the number of ejaculations that male rats were able to show in a 30-min period. By contrast, stimulation delivered to the CP inhibited sexual behavior by slowing its display. Each effect was more pronounced at low than at high stimulation frequencies. In the same rats, once sexually exhausted, electrical stimulation of these brain areas did not reverse the sexual behavior inhibition that characterizes the sexual exhaustion state. It is concluded that dorsal and ventral striatal DA brain regions exert opposite influences on copulatory behavior expression of sexually experienced male rats. Also, that the facilitative effect of NAcc electrical stimulation on sexual activity, with the stimulation parameters used, cannot surmount the sexual behavior inhibition resulting from copulation to satiation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between circadian changes in spontaneous motor activity and dorsal versus ventral striatal dopamine neurotransmission assessed with on-line microdialysis.

The relationship between circadian changes in spontaneous motor activity in rats and dopamine (DA) neurotransmission in the dorsal or ventral striatum was assessed with on-line in vivo microdialysis. The concentration of DA and DA metabolites in the dorsolateral caudate nucleus increased significantly at night. In contrast, DA in the nucleus accumbens did not change significantly across the light–dark cycle. The concentration of DA metabolites in the nucleus accumbens did show circadian variation, however, which was comparable with that seen in the dorsolateral caudate nucleus. Although there was a significant positive correlation between the concentration of DA in both the dorsal and ventral striatum and spontaneous nocturnal motor activity, the relationship was very weak, especially for the accumbens. This suggests that regulating the level of spontaneous motor activity per se is not a primary function of the mesostriatal DA system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased extracellular dopamine in the nucleus accumbens and striatum of the female rat during paced copulatory behavior.

Five groups of ovariectomized rats were tested during in vivo microdialysis, and concentrations of dopamine (DA) and its metabolites were determined in dialysate. In striatum, DA increased more in hormone-primed ovariectomized female rats pacing copulation than in those engaging in sex that could not pace, those that were hormone primed but tested without a male present, or oil-treated groups. Administration of estrogen before microdialysis resulted in enhanced striatal DA in response to a male rat relative to the animals tested without a male. Female rats that were pacing sexual behavior also exhibited a greater increase in accumbens DA than did the no-male, estrogen-primed, or oil-treated groups. Nonpacing animals displayed a significant decrease in DA from accumbens 30 min after introduction of the male rat but otherwise were not different from pacing animals. Estrogen-treated animals also had an enhanced increase in accumbens DA compared with oil-treated rats. These data suggest that DA release in the striatum and accumbens is dependent on the context in which sexual behavior occurs and that estrogen may in part modulate these dopaminergic responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regional decreases in alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) and 6-[3H]cyano-7-nitroquinoxaline-2,3-dione ([3H]CNQX) binding in response to chronic low-level lead exposure: reversal versus potentiation by chronic dopamine agonist treatment

This study evaluated the hypotheses that in vivo lead (Pb) exposure would alter alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor binding and, based on known glutamate-dopamine interactions and Pb-induced changes in dopamine (DA) systems, that AMPA binding might be differentially influenced by DA agonist treatment under conditions of Pb exposure. Alterations in high-affinity ([3H]AMPA) versus total AMPA [6-[3H]cyano-7-nitroquinoxaline-2,3-dione ([3H]CNQX)] receptor binding were determined in medial frontal cortex, dorsal striatum, and nucleus accumbens of rats exposed to 0, 50, or 150 ppm of Pb acetate for 2 weeks or 8 months. Additional 8-month groups received chronic intermittent treatment with saline, the D1 agonist SKF82958, or the general DA agonist apomorphine. Two-week exposures increased AMPA receptor densities, whereas robust decreases occurred after 8 months of Pb; at the latter time point changes were more pronounced for high-affinity than total AMPA receptor binding, with high-affinity effects expressed preferentially in dorsal striatum and nucleus accumbens. DA agonist treatments almost fully reversed Pb-related declines in [3H]AMPA binding but either had no effect (apomorphine) or even further potentiated (SKF82958) the decreases in [3H]CNQX binding. One possible basis for the long-term (8-month) decrease in AMPA binding is a postsynaptic glutamatergic stimulation of non-NMDA receptors.     

Age-related changes in the capacity, rate, and modulation of dopamine uptake within the striatum and nucleus accumbens of Fischer 344 rats: an in vivo electrochemical study

Age-related changes in the capacity, rate, and modulation of dopamine (DA) uptake within the striatum and the nucleus accumbens core of Fischer 344 rats were investigated using in vivo electrochemical recordings coupled with local drug application techniques. Equimolar amounts of DA were pressure ejected into the striatum and the nucleus accumbens of 6-, 12-, 18-, and 24-month old rats. The DA ejections produced larger DA signal amplitudes in the older rats, suggesting age-related differences in the capacity to clear extracellular DA. Within the striatum, the capacity and rate of DA uptake were reduced by 50% in the aged groups (18 and 24 months) compared with the younger rats (6 and 12 months). In the nucleus accumbens, significant reductions in DA uptake capacity and rate were observed in the 24-month group. In both brain regions and in all age groups studied, the rate of DA uptake was found to be concentration-dependent until a maximal rate was reached. The maximum rate of DA transport was significantly reduced in both the striatum and the nucleus accumbens of aged rats (18 and 24 months versus 6 and 12 months). The ability of nomifensine, an inhibitor of the DA transporter, to modulate DA signal amplitudes in the striatum and the nucleus accumbens was also decreased with age (24 months versus 6 months). Taken together, these findings demonstrate substantial age-related deficits in DA uptake processes within the striatum and the nucleus accumbens, consistent with the hypothesis that DA uptake may be slowed in aged animals to compensate for reductions in DA release.     

Effect of scopolamine on the efflux of dopamine and its metabolites after clozapine, haloperidol or thioridazine

The extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum and the nucleus accumbens were measured in awake, freely-moving rats. Clozapine (20 mg/kg, i.p.) increased extracellular DA and HVA in both regions but increased DOPAC only in the striatum. Scopolamine (1 mg/kg), although it had no effect by itself in the striatum or nucleus accumbens, inhibited the ability of clozapine to increase extracellular DA, DOPAC and HVA concentrations in the striatum. The clozapine-induced increase in DA in the frontal cortex was not blocked by scopolamine. Haloperidol (1 mg/kg, i.p.) and thioridazine (10 mg/kg, i.p.) also increased extracellular DA, DOPAC and HVA in the striatum, but scopolamine pretreatment did not inhibit these increases. The results suggest that clozapine differs from haloperidol and thioridazine in that the effect of clozapine, but not that of the two neuroleptic drugs, to increase DA release in the striatum acutely depends on muscarinic receptor stimulation. These results suggest that clozapine, despite its strong muscarinic antagonist properties, does not produce full blockade of muscarinic receptors in vivo in the striatum. The interaction of clozapine with the cholinergic system in the striatum could be relevant to its lack of ability to produce extrapyramidal symptoms or tardive dyskinesia.     

Effect of morphine applied by intrapallidal microdialysis on the release of dopamine in the nucleus accumbens

The effect of morphine, administered intrapallidally, on extracellular concentrations of DA, DOPAC, and HVA in the nucleus accumbens and striatum was studied in the behaving rat using the in vivo microdialysis technique. Unilateral application of morphine hydrochloride was performed through microdialysis probes into the rat ventral pallidum (10 microliters of 0, 2.6, 4.0, 13.0, and 26.0 mM) or globus pallidus (10 microliters of 0 and 26.0 mM). The levels of DA, DOPAC, and HVA were measured using the HPLC with EC detection in dialysates collected from the nucleus accumbens, anteromedial, and anterolateral striatum. Samples were taken every 45 min over 3 h before and over 5 h after morphine or vehicle administration. Administration of morphine into the ventral pallidum resulted in increased DOPAC and HVA concentrations in the nucleus accumbens. Pretreatment with naloxone (1 mg/kg, SC) abolished this effect of morphine. Administration of morphine into the globus pallidus resulted in increased DA, DOPAC, and HVA concentrations in the nucleus accumbens and DA in the anteromedial striatum. The levels of DA and metabolites in anterolateral striatum remained rather unchanged following morphine administered into the ventral pallidum or the globus pallidus. The changes in DA neurotransmission into the nucleus accumbens induced by morphine application into the ventral pallidum and globus pallidus are reminiscent of a phasic and tonic release of DA respectively. The results show that intrapallidal morphine increases DA neurotransmission in nucleus accumbens and suggest that the effect of morphine is mediated by ventral pallidum/mesolimbic and globus pallidus/thalamocortical pathways, depending on the site of injection.     

Efficacy of taxol in the orpk mouse model of polycystic kidney disease

Studies on conscious Sprague-Dawley rats using intracerebral dialysis in live animals combined with high-performance liquid chromatography with electrochemical detection showed that administration of apomorphine into the nucleus accumbens decreased the levels of dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the extracellular space of the dorsal striatum throughout the observation period and produced a transient reduction in the level of homovanillic acid in the dialysate from this structure. The studies demonstrated that reversible exclusion of the nucleus accumbens with procaine produced a transient increase in the levels of dopamine metabolites, without an increase in serotonin metabolites, in the extracellular space of the dorsal striatum. These results demonstrate that the nucleus accumbens affects dopamine metabolism in the striatum, this being mediated by the dopamine-reactive system in the nucleus accumbens.     

Regional differences in the effects of amphetamine withdrawal on dopamine dynamics in the striatum. Analysis of circadian patterns using automated on-line microdialysis

The purpose of the study is to determine the relationship between behavioral symptoms of amphetamine withdrawal and the extracellular concentration of dopamine (DA) in the dorsolateral caudate nucleus and the nucleus accumbens across the entire light-dark cycle. This was accomplished using automated on-line microdialysis sampling in behaving rats. Animals were pretreated with escalating doses of d-amphetamine (or saline) over a 6-week period and then were withdrawn from amphetamine for 3, 7, or 28 days before testing. There were regional differences in the effects of amphetamine withdrawal on the concentrations of DA and DA metabolites in dialysate. Early during withdrawal (3 and 7 days), when animals showed postamphetamine withdrawal behavioral depression (nocturnal hypoactivity), there was a significant decrease in DA and DA metabolites in the dorsolateral caudate nucleus and a disruption in the normal circadian pattern of DA activity. In contrast, there was no effect of amphetamine withdrawal on DA dynamics in the nucleus accumbens. By 28 days after the discontinuation of amphetamine pretreatment, after basal DA in the caudate returned to normal, there was a significant increase in basal DA metabolism in both the caudate and the accumbens. This increase in DA metabolism may be related to the expression of sensitization, including a hypersensitivity to an amphetamine challenge. It is concluded that the role of the dorsal striatum in psychostimulant drug withdrawal syndromes deserves further consideration.     

Dopamine release in the medial preoptic area of female rats in response to hormonal manipulation and sexual activity.

Dopamine (DA) is responsive to hormonal manipulations and has been implicated in the regulation of female rat sexual behavior. In the present studies, extracellular DA levels were assessed in the medial preoptic area (MPOA) of ovariectomized female rats in response to exogenous ovarian hormones and during sexual activity. In female rats primed with a low dose of estradiol benzoate (2 μg), but not with a higher dose (20 μg), a 500-μg progesterone injection increased extracellular DA and facilitated copulatory behavior. Extracellular DA levels in the MPOA were further augmented during sexual interactions with a male rat in a nonpacing copulatory chamber by either perineal or vaginal stimulation. However, in a pacing chamber, DA efflux did not increase, although the metabolites rose significantly during copulation. Together, these findings suggest that extracellular DA in the MPOA responds to the hormonal state of the female rat and may contribute to her expression of sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of olfactory stimuli during copulation in male and female rats.

Describes 3 experiments with a total of 74 gonadally-normal male and 29 ovariectomized female Long-Evans rats. Male and female reactions toward odors from novel and original partners were observed prior to the male's attaining his 1st or 2nd ejaculation. The male's reaction depended upon the sexual condition of the female. Only prior to their initial ejaculation did the males prefer their original partner's odors to those of novel females and only if the odors were collected from the females prior to copulation. This finding corresponded with observations of the male's random choice of partner during copulation. Females responded nonpreferentially if they had copulated prior to testing and showed a marked decrease in responsiveness as copulation continued. Prior to copulation females preferred the odors from males which had not copulated to those of males which had. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Local activation of metabotropic glutamate receptors inhibits the handling-induced increased release of dopamine in the nucleus accumbens but not that of dopamine or noradrenaline in the prefrontal cortex: comparison with inhibition of ionotropic receptors

On-line in vivo microdialysis was used to determine the effects of a 16-min handling period on release of dopamine (DA) in the nucleus accumbens and of DA and noradrenaline (NA) in the medial prefrontal cortex of awake, freely moving rats. DA and NA were determined in one HPLC run. Handling resulted in an immediate and strong increase of both catecholamines in the prefrontal cortex. Maximal values for DA were 295%, and for NA 225%, of controls. DA in the nucleus accumbens was also increased (to 135% of controls) but only after a short delay. Local inhibition of ionotropic glutamate receptors by continuous reversed dialysis of the drugs 6-cyano-7-nitroquinoxaline, D-2-amino-5-phosphonopentanoic acid, or dizocilpine did not significantly affect handling-induced increases in cortical DA and NA release. Neither did the agonist of metabotropic glutamate receptors, trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), or the GABA-B agonist baclofen. Reversed dialysis of dizocilpine in the nucleus accumbens was equally ineffective, but ACPD inhibited the increase in DA release in this area. Stimulation of metabotropic glutamate receptors in the nucleus accumbens was previously reported to inhibit activation of DA release in that area after stimulation of glutamatergic or dopaminergic afferents. It is concluded that metabotropic receptors in the nucleus accumbens are important for the control of activation of DA release in the accumbens by physiological stimuli but that a similar mechanism is lacking in the prefrontal cortex.     

Neurogenesis in the mammalian neostriatum and nucleus accumbens: parvalbumin-immunoreactive GABAergic interneurons

We study the neurogenesis of a distinct subclass of rat striatum gamma-aminobutyric acid (GABA)ergic interneurons marked by the calcium-binding protein parvalbumin (PV). Timed pregnant rats are given an intraperitoneal injection of bromodeoxyuridine (BrdU), a marker of cell proliferation, on designated days between embryonic day (E) 11 and E22. Birthdate of PV neurons is determined in the adult neostriatum and nucleus accumbens by using a BrdU-PV double-labeling immunohistochemical technique. PV-immunoreactive interneurons of the neostriatum show maximum birthrates (>10% double-labeling) between E14-E17, whereas PV-immunoreactive interneurons of the nucleus accumbens show maximum double-labeling between E16-E19. In the neostriatum, caudal PV-immunoreactive neurons are born before those at rostral levels, and lateral PV-immunoreactive neurons become postmitotic before medial neurons. In the postcommissural striatum, ventral PV-immunoreactive neurons become postmitotic before dorsal neurons. In the precommissural striatum, ventral neurons are born before dorsal neurons laterally, but a dorsoventral gradient is seen medially. At corresponding coronal levels, PV-immunoreactive neurons of the nucleus accumbens are born shortly after PV neurons of the neostriatum. Analysis of BrdU labeling intensity in the nucleus accumbens shows that medium spiny projection neurons of the shell become postmitotic before neurons of the core. Similarly, PV-immunoreactive interneurons of the nucleus accumbens shell are born before PV interneurons of the core. Compared with cholinergic interneurons of the neostriatum, PV-immunoreactive interneurons are born later, but neurogenetic gradients are similar. The period of striatum PV interneuron genesis encompasses the period for somatostatin interneurons, although the latter neurons do not show neurogenetic gradients, possibly due to heterogeneous subtypes. Consideration of basal telencephalon neurogenesis suggests that subpopulations of striatum interneurons may share common neurogenetic features with phenotypically similar populations in the basal forebrain, with final morphology and connectivity depending on local cues provided by the host environment.     

c-Fos immunoreactivity in the sexually dimorphic area of the hypothalamus and related brain regions of male gerbils after exposure to sex-related stimuli or performance of specific sexual behaviors

The sexually dimorphic area of the gerbil hypothalamus is essential for male sex behavior. To determine which aspects of mating activate its cells, or cells near or connected to it, we visualized c-Fos in the brains of male gerbils that had been exposed to various types of sex-related stimuli or that had displayed various aspects of sex behavior. Five groups of males were placed in familiar arenas containing sex-related odors. All subjects had previously mated in these arenas. For four groups, a female was introduced and remained with the male until he ejaculated, intromitted, mounted or sniffed her. Males in the fifth group remained in the arena alone. Males in a sixth group were placed in a clean arena in another room. These males were also familiar with this arena but had never encountered a female there. The seventh group remained in their home cages. The posterodorsal preoptic nucleus, the lateral part of the posterodorsal medial amygdala, the medial part of the sexually dimorphic area and the parvicellular part of the subparafascicular nucleus of the thalamus expressed c-Fos after ejaculation. Whether these cells triggered ejaculation or responded to it is not clear. The latter two areas also expressed c-Fos whenever males were exposed to the sex arena, but the sexually dimorphic area pars compacta did not express c-Fos under any condition. The medial core of the nucleus accumbens, the ventrolateral septum, the caudomedial bed nucleus of the stria terminalis, the medial/central part of the posterodorsal medial amygdala and the lateral part of the sexually dimorphic area also expressed c-Fos when males entered the sex arena. The ventrolateral part of the ventromedial nucleus of the hypothalamus expressed c-Fos whenever males were with females. None of the 31 areas studied responded to mounting or intromission, but the zona incerta, the amygdalohippocampal area, the lateral part of the sexually dimorphic area and the area lateral to the medial part of the sexually dimorphic area showed progressive increases in c-Fos expression as mating progressed. The area dorsal to the medial part of the sexually dimorphic area, the paraventricular nucleus of the hypothalamus, the ventral premammillary nucleus and the retrorubral field showed the same level of c-Fos expression when males were exposed to the non-sexual context as when they were exposed to the sexual one. While a projection to the retrorubral field from the sexually dimorphic area is critical for male sex behavior, the retrorubral field did not show a sex-related c-Fos response. The data suggest that brain regions involved in male sex behavior are involved in different aspects of it and that this can also apply to different subsets of cells in each area. The data also indicate that cells involved in mating do not necessarily show mating-related patterns of c-Fos expression. Thus, while c-Fos is useful for identifying areas involved in mating, or other behaviors, its characteristics could cause relevant areas to be overlooked.     

Sex differences in ethanol-induced dopamine release in nucleus accumbens and in ethanol consumption in rats

In vivo microdialysis was used to examine changes in nucleus accumbens and striatal dopamine, dihydrophenylacetic acid (DOPAC), and homovanillic acid (HVA) following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in male and female Long-Evans rats. Following dialysis, rats were trained to bar-press for oral ethanol reinforcement. In nucleus accumbens, females showed significant increases in extracellular dopamine following 0.25 or 0.5 g/kg ethanol, but did not show significant increases over baseline at the higher doses. Males showed slight increases in dopamine at the lower doses and decreased dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in striatal metabolite levels. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. The pattern of both greater ethanol-induced nucleus accumbens dopamine release and greater ethanol consumption in females supports the hypothesis that ethanol reward is mediated, at least in part, by the mesolimbic dopamine system.     

A hemagglutinin-based multipeptide construct elicits enhanced protective immune response in mice against influenza A virus infection

The effect of the muscarinic antagonist, scopolamine, was examined for a change in the increase in extracellular dopamine, dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA), induced by haloperidol or clozapine in the striatum and nucleus accumbens of anaesthetised and awake rats, monitored using in vivo cerebral microdialysis. Rats received scopolamine (1 mg kg(-1); s.c.) or vehicle followed by haloperidol (1 mg kg(-1); s.c.) or clozapine (20 mg kg(-1); s.c.). Dopamine, DOPAC, HVA and 5-HIAA overflow into striatal or accumbens perfusates was determined using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Scopolamine failed to modify the clozapine- or haloperidol-induced efflux of dopamine or its metabolites in either the striatum or nucleus accumbens following systemic administration in anaesthetised or awake rats. Although pretreatment with scopolamine tended to produce a smaller increase in the clozapine-induced efflux of DOPAC in striatal perfusates than following clozapine treatment alone, this was not statistically significant. Furthermore, local infusion of scopolamine (100 microM) with clozapine (1 mM) via the microdialysis probe did not attenuate the elevated efflux of dopamine observed following clozapine alone, in either the striatum or nucleus accumbens, in anaesthetised rats. This treatment did prevent the clozapine-induced increase in DOPAC and HVA in the striatum but not the nucleus accumbens. Carbachol (50 microM) infused into the dorsolateral striatum or nucleus accumbens raised extracellular dopamine levels 200% and 150%, respectively above baseline. Our data suggest that the increased efflux of dopamine and its metabolites in the rat basal ganglia following clozapine administration is not significantly dependent upon the interaction of clozapine with muscarinic receptors.     

Dopamine and preparatory behavior: II. A neurochemical analysis.

Changes in the activity of dopamine-containing systems in relation to preparatory and consummatory feeding responses were investigated. In Exp 1 rats were conditioned to associate food delivery with the presentation of a conditional stimulus (CS+). When sacrificed after exposure to the CS+ alone on a test trial, the ratio of the dopamine metabolite 3,4-dihydroxyphenylacetic acid to dopamine ({dopac/da} ratio) was increased significantly in the nucleus accumbens. A similar trend in the ratio of homovanillic acid to dopamine ({hva/da} ratio) was also observed. Similar increases were observed in the striatum, but these were not statistically significant. In contrast, no increases were observed in the {dopac/da} ratio or the {hva/da} ratio in either brain region when rats were permitted to consume an unsignaled meal for 7 min. Findings suggest that activation of dopamine terminals in the nucleus accumbens occurs during the anticipation of a meal, at which times the rat is engaged in preparatory feeding behaviors, but does not accompany the performance of short bouts of consummatory feeding behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of vomeronasal organ removal from male mice on their preference for and neural Fos responses to female urinary odors.

Four experiments were conducted to determine whether vomeronasal organ (VNO) inputs in male mice mediate the rewarding properties of estrous female urinary odors. Sexually naive male mice with either an intact (VNOi) or lesioned (VNOx) VNO preferred to investigate female urine over water in Y-maze tests. Subsequently, VNOi males ran significantly more quickly and remained in nasal contact longer with estrous female urine than with male urine, whereas VNOx males investigated these odors equally. In home-cage habituation-dishabituation tests, VNOi males also investigated female urine significantly longer than did VNOx males, although both groups investigated female urine longer than other non-body odors. Finally, female urinary odors induced Fos in the nucleus accumbens core of VNOi males but not of VNOx males. Our results suggest that female urinary odors retain some incentive value in VNOx males. However, once direct nasal contact is made with female urine, VNO inputs further activate forebrain mechanisms that amplify the reward salience of this stimulus for the male mouse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine and serotonin release-regulating autoreceptor sensitivity in A9/A10 cell body and terminal areas after withdrawal of rats from continuous infusion of cocaine

The effects of dopamine (DA) and 5-hydroxytryptamine (5-HT) autoreceptor agents on electrically induced [3H]DA and [3H]5-HT release from superfused slices of striatum, nucleus accumbens and ventral mesencephalon (VM) containing A9 and A10 neurons were investigated in rats made tolerant to the stimulatory effect of cocaine on locomotor behavior by a 14-day continuous infusion of cocaine (29 mg/kg/day) by s.c. implanted osmotic minipumps followed by a 7-day drug-free period. In VM, electrically induced [3H]DA was increased, the ability of pergolide to inhibit this release was abolished, but the ability of sulpiride to facilitate the release was potentiated, implicating a higher concentration of synaptic DA modifying the responsiveness of somatodendritic D2 autoreceptors to D2 agents. Both electrically induced [3H]5-HT release from VM and the stimulatory effect of in vitro cocaine on this release were enhanced whereas the effects of both 5-methoxytryptamine and methiothepin were attenuated, indicating that subsensitivity of 5-HT autoreceptors developed in DA cell body regions. In striatum and nucleus accumbens, no significant changes were observed in [3H]DA and [3H]5-HT release, except for a modest reduction in the effects of both pergolide and sulpiride on electrically induced [3H]DA release from striatum. These results emphasize the importance of pretreatment-induced changes in DA cell body regions, rather than terminal areas, under the present conditions. The observed increase in DA autoinhibitory tone and subsensitivity of 5-HT release-regulating autoreceptors in the VM may contribute to the locomotor tolerance upon cocaine challenge after continuous cocaine.     

Regional changes in dopamine and serotonin activation with various intensity of physical and psychological stress in the rat brain

The present study examined whether regional patterns of brain dopamine (DA) and serotonin (5-HT) activation after physical and psychological stress depend on the intensity of that stress. Monoamine concentrations (DA, 5-HT, and their metabolites) were measured using high-performance liquid chromatography with electrochemical detection in eight brain regions of rats exposed to two different intensities of foot shock stress for 30 min (1.5 mA or 2.5 mA) or conditioned fear stress (CFS, after single or repeated foot shock). A low level of foot shock selectively increased the DA metabolism in the medial prefrontal cortex (mPFC), whereas a high level of foot shock increased it in most of the brain regions examined in the present study. A low level of foot shock did not increase the 5-HT metabolism in any regions, but a high-intensity shock increased the 5-HT metabolism in the mPFC, nucleus accumbens, and lateral hypothalamus. Rats that received high-intensity shock displayed more freezing than those that received low-intensity shock in a conditioned fear paradigm (24 h after receiving foot shock, the animals were placed in a shock chamber without being given shock), indicating an augmentation of conditioned fear. The increased DA and 5-HT metabolism were especially marked in the mPFC after CFS following a single foot shock session (2.5 mA). Rats that were repeatedly exposed to 2.5 mA foot shock for a period of 10 days displayed a greater degree of freezing induced by CFS than those given only one foot shock session, indicating an augmentation of fear and stress intensity. CFS after repeated foot shock, like foot shock per se, increased the DA metabolism in most of the brain regions except for the striatum and increased the 5-HT metabolism in the mPFC, nucleus accumbens, and amygdala. These results suggest that regional patterns of brain DA and 5-HT activation after physical and psychological stress depend on the intensity of that stress, although there are some differences between these stress; and that the more widespread activation of DA and 5-HT after more severe stress might relate to behavioral changes that reflect the augmentation of fear.