Identification and characterization of CDS2, a mammalian homolog of the Drosophila CDP-diacylglycerol synthase gene

The technique of intracranial microdialysis was used to investigate the effects of aging on the striatal dopaminergic system of the anesthetized Fischer 344 rat. Microdialysis probes were implanted into the striatum of young (2-8 months) and aged (24-28 months) urethane anesthetized rats. Striatal dialysate levels were analyzed for dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and serotonin (5-HT) by high performance liquid chromatography with electrochemical detection. As compared to the young animals, basal extracellular levels of DA and DOPAC were significantly decreased in two groups of aged animals. Stimulation with excess potassium added through the microdialysis probe produced a robust overflow of DA in the young and aged rat striatum, but the evoked overflow of DA was not diminished in the aged rat striatum as compared to young animals. In contrast, d-amphetamine-evoked overflow of DA was again robust in young and aged animals, but was greatly decreased in the aged rat striatum as compared to the signals recorded in the young rats. Taken together with previous reports, these data support the hypothesis that a major change in the regulation of DA release that occurs in aging involves changes in the function of the neuronal uptake of DA, which may be a compensatory property of DA neurons in senescence.     

Simultaneous determination of an active metabolite and open-ring metabolites by high performance liquid chromatography and pharmacokinetic studies of a penem antibiotic, FCE22891, in dogs

The participation of N-methyl-d-aspartate (NMDA) receptors on dopamine (DA) efflux in the striatum of anaesthetized rats, which had their DA nigrostriatal pathway previously lesioned with different doses of 6-hydroxydopamine (6-OH-DA), was assessed by in vivo microdialysis methodology. In addition, the in vivo basal DA and dihydroxy-phenyl-acetic acid (DOPAC) effluxes and the effect of local K+-depolarization on DA release were also evaluated in the striatum of these 6-OH-DA treated rats. Lesioned rats were divided in three groups corresponding to animals with 25-75%, 75-95% and >95% of striatum tissue DA depletion, respectively. Striatal DA tissue depletion between 25-75% occurred in parallel with a 30% reduction in DA extracellular levels, with a moderate 10% increase in basal fractional DA efflux, and with no statistical changes in the fractional DA efflux induced by NMDA (500 microM) receptor stimulation by reverse dialysis. Rats with higher DA tissue depletion (between 75-95%) exhibited a 60% reduction in DA extracellular levels in the striatum and this reduction occurred in parallel with a modest rise in basal fractional DA efflux, but with a striking decrease in the NMDA-induced fractional DA efflux. In rats with extreme or >95% of striatal DA tissue depletion, basal fractional DA efflux in the striatum increased quite substantially along with a recovery in the ability of NMDA receptor stimulation to induce fractional DA release. The >95% striatal DA-depleted rats also exhibited a significant decrease in tissue and extracellular DOPAC/DA ratio when compared to sham and partially DA-depleted rats. In contrast to the previous results, fractional DA efflux induced by reverse dialysis with K+ (40 mM) remained the same in the striatum of sham and all groups of DA-tissue depleted rats. The present findings suggest the existence of at least three features associated to the regulation of basal and NMDA-induced extracellular levels of DA in the striatum of rats as a function of striatal tissue DA depletion produced by 6-OH-DA. They also support the view that a differential regulation of basal and NMDA-induced DA extracellular levels occur in partial and extreme DA-depleted striatum after 6-OH-DA treatment. Such findings may have implications as regard to the participation of the NMDA receptor in the compensatory mechanisms associated to the progress of Parkinson's disease, as well as in the therapeutic treatment of this neurological disorder.     

Effect of repeated methamphetamine administrations on dopamine and glutamate efflux in rat prefrontal cortex

Pretreatment with psychostimulants such as methamphetamine (METH) results in augmented mesostriatal dopamine transmission upon a challenge administration of the drug. This effect can be blocked by dopamine antagonists and excitatory amino acid antagonists. However, no direct comparisons have been made with respect to the effects of a low-dose pretreatment regimen of METH on impulse and transporter-mediated dopamine release or to what extent glutamate release is altered by a pretreatment regimen with METH. The purpose of this study was to examine dopamine and glutamate efflux in the prefrontal cortex and striatum in rats pretreated with METH following either high potassium (80 microM) infusion or after a systemic injection of a low dose of METH. Extracellular dopamine and glutamate concentrations in the prefrontal cortex and striatum were measured in vivo by microdialysis. Potassium infusion increased extracellular dopamine and glutamate concentrations to a greater extent in the prefrontal cortex than in the striatum of METH-pretreated rats compared to saline-pretreated controls. A low dose METH challenge significantly increased extracellular dopamine but not glutamate concentrations in both prefrontal cortex and striatum of all animals. Moreover, the acute METH-induced increased in cortical dopamine efflux was significantly greater in rats pretreated with METH. Overall, these data are the first evidence that repeated METH administrations can enhance cortical glutamate efflux and indicate that a low dose pretreatment regimen of METH enhances dopamine transmission in the prefrontal cortex through both transporter and depolarization-induced mechanisms.     

Regional differences in striatal dopamine uptake and release associated with recovery from MPTP-induced parkinsonism: an in vivo electrochemical study

This study directly assessed striatal dopamine (DA) uptake rates and peak release in response to KCl in normal, symptomatic, and recovered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cats using in vivo electrochemistry. DA uptake rates measured after direct application of known concentrations of DA to the striatum were slowed significantly in both dorsal and ventral striatum in symptomatic cats compared with rates recorded in normal animals. DA uptake rates remained significantly slowed in recovered cats and were not significantly different from the rates recorded in symptomatic animals. In symptomatic cats, both DA uptake rates and the signal recorded in response to KCl stimulation were significantly decreased from normal in all dorsal and ventral striatal regions sampled. Reduction/oxidation (redox) ratios recorded in response to KCl stimulation suggested DA to be the predominant electroactive species. In spontaneously recovered MPTP-treated cats, recordings in the ventral striatum subsequent to KCl stimulation again suggested DA to be the predominant electroactive species released, and peak levels were significantly higher than those recorded in symptomatic animals. In the dorsal striatum of recovered cats, redox ratios recorded subsequent to KCl stimulation suggested serotonin rather than DA to be the predominant electroactive species released. Peak levels of release in the dorsal striatum were not significantly greater than those recorded in symptomatic animals. These results suggest that in spontaneously recovered MPTP-treated cats, there is partial recovery of ventral striatal DAergic terminals, persistent loss of dorsal striatal DAergic terminals, and a down-regulation of DA transporter number/function throughout the striatum. These processes may contribute to volume transmission of DA in the striatum and promote functional recovery.     

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)     

A chemiluminescent microtiter plate assay for sensitive detection of protein kinase activity

The toxic effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/kg) and methylenedioxymethamphetamine (MDMA) (5.0, 10.0 and 20.0 mg/kg) on dopaminergic systems were assessed in the striatum and of the nucleus accumbens in mdr1a wild-type and knockout mice. METH caused significant dose-dependent decreases of dopamine (DA) and DA transporters (DAT) in the striatum and the nucleus accumbens (NAc) of both wild-type and knockout mice. The lowest doses of METH (2.5 mg/kg) caused only small changes in the wild-type, but marked. decreases in the mdr1a knockout mice. The two higher doses (5 mg/kg and 10 mg/kg) caused similar changes in both strains of mice. In contrast to METH, MDMA caused greater percentage decreases in DAT in the wild-type mice. For example, the lowest dose (5 mg/kg) caused significant decreases in DAT in the NAc of wild-type but not of mdr1a knockout mice. The highest dose (20 mg/kg) caused similar changes in both the strains. These results suggest that METH and MDMA interact differentially with P-glycoproteins. These observations document, for the first time, a role for these proteins in the entry of METH and MDMA into the brain via the blood-brain barrier, with P-glycoprotein possibly facilitating the entry of MDMA but interfering with that of METH into the brain.     

Dual-earner families: the importance of work stress and family stress for psychological well-being

The effect of neonatal hippocampal lesions on behavioral sensitivity to amphetamine (AMPH) and dopamine (DA) release in the nucleus accumbens (NAc) were examined. The ventral hippocampus was damaged bilaterally by ibotenic acid on postnatal day 7 (PD7). Spontaneous exploration and AMPH-stimulated locomotor activity were examined on postnatal day 35 (PD35) and day 56 (PD56). Extracellular DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were sampled using in vivo microdialysis while simultaneously AMPH-stimulated locomotion was examined in freely moving rats on PD56. Spontaneous exploration increased in rats with hippocampal lesions relative to controls on PD56 but not PD35. AMPH (0, 0.187, 0.375, 0.75, 1.5, and 3 mg/kg) enhanced locomotion dose-dependently in both control and lesioned groups. Locomotor activity was higher in lesioned rats than controls following AMPH at the dose of 0.75 mg/kg on PD35 and at the doses of 1.5 and 3.0 mg/kg on PD56. The basal level of DA in the NAc was not different between the hippocampal and control groups. AMPH (1.5 mg/kg) induced hyperlocomotion in lesioned rats relative to controls. DA release in the NAc for both groups was enhanced following injections of AMPH. However, neonatal hippocampal lesions had no further enhancement on AMPH-stimulated release of DA as compared to the control group. The levels of DOPAC and HVA in the NAc were altered by AMPH but not lesions. The level of 5-HIAA was not influenced by either lesions or AMPH. The results of neonatal lesion-induced hyperlocomotion suggest that an emergence of behavioral hyperresponsiveness to AMPH was dependent on an interaction of lesions, age of examination, and dose of the drug. A dissociation between the effect of AMPH on lesion-enhanced hyperlocomotion and a lack of a lesion-enhanced DA release in the NAc suggest that presynaptic release of DA had no major contribution to lesion-enhanced DA transmission in the mesolimbic DA system.     

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.     

Short- and long-term effects of perinatal asphyxia on monoamine, amino acid and glycolysis product levels measured in the basal ganglia of the rat

The effects of perinatal asphyxia on levels of dopamine (DA) and its metabolites, amino acids and glycolysis products, measured in tissue samples from substantia nigra (SN), striatum, ventral tegmental area (VTA), and nucleus accumbens (Acb), were studied 80 min to 8 days after birth with high performance liquid chromatography (HPLC). Furthermore, extracellular levels of DA, amino acids and glycolysis products were measured with in vivo microdialysis in the striatum 40-140 min and 4 weeks after birth. Asphyxia was induced by immersing foetus-containing uterus horns, removed from ready-to-deliver Sprague-Dawley rats, in a water bath at 37 degrees C for various time periods (0-22 min). Spontaneous- and caesarean-delivered pups were used as controls. Perinatal asphyxia led to a decrease in the rate of survival, depending upon the length of the insult. In parallel, lactate (LACT) levels were increased with the length of the insult in all examined brain regions, monitored ex vivo or in vivo immediately after birth. DA, glutamate (GLU) and aspartate (ASP) levels were also increased, mainly in tissue samples taken from the mesencephalon. Only minor changes were observed in tissue samples taken from the telencephalon. However, in experiments with in vivo microdialysis, DA and GLU levels were increased following 20-21 and 21-22 min of perinatal asphyxia, but the effect of K+ depolarisation on extracellular DA and ASP levels was strongly diminished. DA and metabolites increased with development in SN and striatum, with no clear differences between control and asphyctic rats. However, 8 days after birth, it was found that DA levels were increased, alternatively decreased in mesencephalic and telencephalic regions following 20-21 and 21-22 min of perinatal asphyxia, periods associated with 60% and 90% of perinatal mortality, respectively. Furthermore, in microdialysis experiments performed 4 weeks after birth, extracellular DA and its metabolites levels were also increased, alternatively decreased in rats exposed to a 20-21 and 21-22 min perinatal asphyctic insult. In this last group, GLU and ASP levels were also decreased. Furthermore, the effect of K+ depolarisation on DA and ASP levels was strongly decreased in both asphyctic groups. Thus, perinatal asphyxia produces short- and long-term consequences in general metabolism, and induces region-specific changes in several neurotransmitter systems, mainly affecting meso-telencephalic DA systems.     

Serotonin 5-HT2C agonists selectively inhibit morphine-induced dopamine efflux in the nucleus accumbens

In vivo microdialysis was used to compare the effects of serotonergic drugs on morphine- and cocaine-induced increases in extracellular dopamine (DA) concentrations in the rat nucleus accumbens (NAc). Systemic administration of the 5-HT2A/2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg, s.c. ) prevented the increase in extracellular DA in the NAc produced by morphine (5 mg/kg, i.p.). In contrast, this dose of DOI had no effect on the ability of cocaine (10 mg/kg, i.p.) to increase extracellular DA concentrations in the NAc. A 5-HT2C selective agonist, 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212, 5 mg/kg, s.c.) also inhibited morphine-induced increases in extracellular DA concentrations in the NAc. Pretreatment of rats with the selective 5-HT2A antagonist, amperozide, had no effect on morphine-induced elevation of NAc DA concentrations. In order to determine if inhibition of the firing of 5-HT neurons contributes to the serotonin agonist-mediated inhibition of morphine-induced accumbens DA release, rats were pretreated with the 5-HT1A agonist, 8-OHDPAT. At a dose of 100 microg/kg (sc), 8-OHDPAT did not interfere with morphine's ability to increase DA concentrations in the NAc. These results suggest that the activation of 5-HT2C receptors selectively inhibits morphine-induced DA release in the NAc in a manner which is independent of the inhibition of 5-HT neurons.     

Electrical stimulation of the medial prefrontal cortex increases dopamine release in the striatum

Exogenous and endogenous glutamate has been shown to evoke dopamine (DA) release in the striatum using both in vitro and in vivo techniques. We hypothesized that stimulation of the prefrontal cortex (PFC) would phasically enhance striatal DA release via the glutamatergic corticostriatal pathway. To test this hypothesis, in vivo brain microdialysis was employed to measure extracellular concentrations of DA in the striatum during electrical stimulation of the PFC. Five rats were implanted with bilateral electrodes located in the medial PFC and dialysis probes in the dorsal striatum. Two days later the PFC of these awake, freely moving rats was stimulated first at 50 microA and then at 100 microA for 20 minutes at 2-hour intervals. Both currents significantly increased DA release. Extracellular DA rose rapidly during stimulation, peaked immediately afterward, and then slowly returned to baseline values. Dopamine reached 118% of baseline values with 50 microA stimulation and 138% with 100 microA stimulation. Histologic analysis using the fluorescent retrograde dye Fluoro Gold confirmed that cells projecting to the vicinity of the striatal dialysis probe originated in the vicinity of the PFC electrodes. These results provide direct evidence for phasic, excitatory modulation of striatal DA release by the PFC.     

Higher plants light harvesting proteins. Structure and function as revealed by mutation analysis of either protein or chromophore moieties

In vivo microdialysis was used to examine the effects of dopaminergic transplants on extracellular concentrations of dopamine (DA), serotonin (5-HT), and their precursors and major metabolites in the denervated rat striatum. Dialysis perfusates were collected from intact 6-hydroxydopamine (6-OHDA) lesion plus sham grafted, and lesion plus fetal substantia nigra (SN) grafted striata. The SN transplants ameliorated the reduction of striatal DA and dihydroxyphenylacetic acid (DOPAC) levels in rats with unilateral 6-OHDA lesions of the mesostriatal pathway. The transplants also increased extracellular levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the denervated striatum. In response to NSD-1015 (an inhibitor of aromatic L-amino acid decarboxylase, AADC), 5-hydroxytryptophan (5-HTP) levels were substantially elevated in the SN grafted striata as compared with those in the sham grafted controls, which continued even after subsequent administration of L-3,4-dihydroxyphenylalanine (L-DOPA, 100 mg/kg i.p.). Immunohistochemical analysis showed hyperinnervation of 5-HT fibers in the grafted striatum, which was consistent with the results of microdialysis experiments. These results indicated that implantation of SN grafts into the 6-OHDA-lesioned striatum of rats induces hyperactivity of 5-HT synthesis, release and metabolism.     

Age, side height, and spindle shape of the crib in climbing over the side

Norepinephrine (NE) was microinjected into the paraventricular nucleus (PVN), while microdialysis was used to monitor extracellular dopamine (DA) and acetylcholine (ACh) in the nucleus accumbens (NAc). The PVN is a site where exogenously administered NE can act through alpha 2 receptors to elicit eating behavior and preference for carbohydrates. It was hypothesized that NE in the PVN acts on a behavior reinforcement system by altering the DA/ACh balance in the NAc. NE microinjections (80 nmol in 0.3 microliter), which effectively elicited feeding in satiated rats in a separate test, caused a significant increase in extracellular DA (109%) and decrease in ACh (-27%) when the same animals were tested in the absence of food. In contrast when the food was available and ingested, ACh increased (51%) instead of decreasing. These results support the hypothesis that a functional link exists between the PVN and the NAc in which DA helps initiate and ACh helps stop appetitive behavior involved in the reinforcement of eating.     

Dopamine release in the nucleus accumbens by hypothalamic stimulation-escape behavior

It is known that lateral hypothalamic stimulation or self-stimulation can release dopamine in the nucleus accumbens (NAc). The present experiment illustrates that an aversively motivated behavior can also do this. Rats were prepared with microdialysis probes in the NAc and electrodes in the lateral hypothalamus (LH) or medial hypothalamus (MH). Automatic stimulation of the LH increased extracellular dopamine in the NAc 30% as reported earlier. The animals would perform both self-stimulation to turn the current on and stimulation-escape to turn it off, suggesting a combination of reward and aversion. Escape responding increased extracellular dopamine (DA) 100%, even though there was less total stimulation. Automatic stimulation of the MH did the opposite of the LH by decreasing accumbens dopamine (-20%), and the animals would only perform stimulation-escape, indicative of pure aversion. But again, extracellular DA in the NAc increased 100% during escape responding. Thus DA can be released during negative reinforcement when an animal's behavior is reinforced by escape from lateral or medial hypothalamic stimulation. This suggests that DA release was correlated with stimulation-escape behavior, rather than the aversiveness of automatic stimulation.     

Dopamine-releasing action of 6R-L-erythro-tetrahydrobiopterin: analysis of its action site using sepiapterin

Recently, we reported that 6R-L-erythro-tetrahydrobiopterin (6R-BH4), a natural cofactor for hydroxylases of tyrosine and tryptophan, has a monoamine-releasing action independent of its cofactor activity. Here we attempted to determine whether 6R-BH4 acts inside the cell or from the outside of the cell by using brain microdialysis in the rat striatum. For this purpose, sepiapterin, and immediate precursor of 6R-BH4 in the salvage pathway, was used to selectively increase the intracellular 6R-BH4 levels. Dialytic perfusion of sepiapterin increased tissue levels of reduced biopterin (mainly 6R-BH4) but not the extracellular levels. Administration of sepiapterin increased the extracellular levels of 3,4-dihydroxyphenylalanine (DOPA) (an index of in vivo tyrosine hydroxylase activity) and of dopamine (DA) (an index of in vivo DA release). Either of the increases was eliminated after pretreatment with a tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine. Administration of 6R-BH4 increased extracellular levels of reduced biopterin. DOPA, and DA. After pretreatment with alpha-methyl-p-tyrosine, the increase in DOPA levels was abolished, but most of the increase in DA levels persisted. The increase in DA levels also persisted after pretreatment with nitric oxide synthase inhibitors. These data demonstrate that 6R-BH4 stimulates DA release directly, independent of its cofactor action for tyrosine hydroxylase and nitric oxide synthase, by acting from the outside of neurons.     

Continuous cocaine induces persisting alterations in dopamine overflow in caudate following perfusion with a D1 agonist

The present study examined whether exposure to 5 days of continuous cocaine in rats would produce any persisting alterations of the decrease in striatal dopamine (DA) overflow produced by local infusion of a D1 receptor agonist. Using a microdialysis probe in striatum, changes in DA, DA metabolites, and GABA were assessed 14 to 21 days following a 5-day continuous cocaine treatment. There were no differences in baseline levels of DA and it's metabolites. SKF 38393 (10(-6) infusion into the striatum decreased striatal DA levels in the controls and this effect was attenuated in cocaine-pretreated rats. This result, together with other observations, supports the hypothesis of a persistently altered D1-mediated negative feedback produced by previous exposure to continuous cocaine.     

Striatal extracellular dopamine levels in rats with haloperidol-induced depolarization block of substantia nigra dopamine neurons

Correlations between substantia nigra (SN) dopamine (DA) cell activity and striatal extracellular DA were examined using simultaneous extracellular single-unit recordings and in vivo microdialysis performed in drug-naive rats and in rats treated repeatedly with haloperidol (HAL). Intact rats treated with HAL for 21-28 d exhibited significantly fewer active DA cells, indicating the presence of depolarization block (DB) in these cells. However, in rats that received surgical implantation of the microdialysis probe followed by a 24 hr recovery period, HAL-induced DA cell DB was reversed, as evidenced by a number of active DA neurons that was significantly higher than that in HAL-treated intact rats and similar to that of drug-naive rats. In contrast, using a modified probe implantation procedure that did not reverse SN DA neuron DB, we found striatal DA efflux to be significantly lower than in controls and significantly correlated with the reduction in DA neuron spike activity. Furthermore, although basal striatal DA efflux was independent of SN DA cell burst-firing activity in control rats, these variables were significantly correlated in rats with HAL-induced DA cell DB. Therefore, HAL-induced DB of SN DA neurons is disrupted by implantation of a microdialysis probe into the striatum using standard procedures. However, a modified microdialysis method that allowed reinstatement of DA neuron DB revealed that the HAL-induced inactivation of SN DA neurons was associated with significantly lower extracellular DA levels in the striatum. Moreover, the residual extracellular DA maintained in the presence of DB may, in part, depend on the burst-firing pattern of the noninactivated DA neurons in the SN.     

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.     

Interaction with pups enhances dopamine release in the ventral striatum of maternal rats: a microdialysis study

A growing body of evidence suggests that an interference with dopamine (DA) transmission disrupts maternal behavior in the rat. The present brain microdialysis study was therefore conducted to investigate whether infants can modulate ventral striatal DA release in mother rats. There was a significant rise in the extracellular concentrations DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the ventral striatum when mothers were reunited with their litters following separation overnight. Nursing was the predominant behavior during this phase of the experiment. More active behaviors were elicited by soiling pups with flowerpot earth, and this was accompanied by further increases in DA, DOPAC, HVA, and 5-HIAA. It is suggested that pup-induced stimulation of ventral striatal DA release facilitates parental responses such as pup retrieval.     

Substrates of energy metabolism attenuate methamphetamine-induced neurotoxicity in striatum

High doses of methamphetamine (METH) produce a long-term depletion in striatal tissue dopamine content. The mechanism mediating this toxicity has been associated with increased concentrations of dopamine and glutamate and altered energy metabolism. In vivo microdialysis was used to assess and alter the metabolic environment of the brain during high doses of METH. METH significantly increased extracellular concentrations of lactate in striatum and prefrontal cortex. This increase was significantly greater in striatum and coincided with the greater vulnerability of this brain region to the toxic effects of METH. To examine the effect of supplementing energy metabolism on METH-induced dopamine content depletions, the striatum was perfused directly with decylubiquinone or nicotinamide to enhance the energetic capacity of the tissue during or after a neurotoxic dosing regimen of METH. When decylubiquinone or nicotinamide was perfused into striatum during the administration of METH, there was no significant effect on METH-induced striatal dopamine efflux, glutamate efflux, or the long-term dopamine depletions measured 7 days later. However, a delayed perfusion with decylubiquinone or nicotinamide for 6 h beginning immediately after the last METH injection attenuated the METH-induced striatal dopamine depletions measured 1 week later. These results support the hypothesis that the compromised metabolic state produced by METH administration predisposes dopamine terminals to the neurotoxic effects of glutamate, dopamine, and/or free radicals.