Immunocytochemical localization of midbrain estrogen receptor- and progestin receptor-containing cells in female guinea pigs

In the guinea pig midbrain, a low concentration of progestin receptors is induced by estradiol. This is in contrast to the mediobasal hypothalamus which has a large number of estradiol-induced progestin receptors. Because the midbrain is an important site for the hormonal regulation of sexual behavior, we mapped the distribution of cells containing estrogen receptor- and estradiol-induced progestin receptor-immunoreactivity in that area. Estrogen receptor-immunoreactive cells are found in midbrain sites previously reported, including the midbrain central gray, the tegmentum lateral and ventral to the central gray, peripeduncular region, and parabrachial nuclei. While progestin receptor-immunoreactive cells were not detected without estradiol priming, estradiol-induced progestin receptors were found throughout the rostrocaudal extent of the midbrain central gray and adjacent tegmental area. Progestin receptor-immunoreactive cells were far fewer than estrogen receptor containing cells, had less cytoplasmic staining, and appeared restricted to the midbrain central gray, lateral and ventrolateral to the cerebral aqueduct and the adjacent tegmental area.     

Effects of medial preoptic–anterior hypothalamic lesions on development of sociosexual behavior in dogs.

Bilateral medial preoptic–anterior hypothalamic lesions in adult male dogs eliminate or impair copulatory behavior and reduce urine-marking responses but do not affect aggressive behavior. The present study examined the emergence of the adult forms of these same male sociosexual behavioral patterns when the lesions were made prior to puberty. 18 beagle puppies were allowed to interact with male peers during development. Ss with lesions had reduced frequency of juvenile mounting and an almost total absence of male copulatory activity in adulthood. Urine-marking and aggressive behavior in the juvenile and adult periods were not affected by the lesions. Findings reveal a sparing of function with regard to urine-marking but not sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Volatile anesthetics do not alter bradykinin-induced release of nitric oxide or L-citrulline in crystalloid perfused guinea pig hearts

Trimethylamine N-oxide (TMAO) is an abundant compound of tissues of marine fish and invertebrates. During fish spoilage, certain marine bacteria can reduce TMAO to nauseous trimethylamine (TMA). One such bacterium has been isolated and identified as a new Shewanella species, and called Shewanella massilia. The anaerobic growth of S. massilia is greatly increased when TMAO is added, indicating that TMAO reduction involves a respiratory pathway. The TorA enzyme responsible for TMAO reduction is a molybdenum cofactor-containing protein of 90 kDa located in the periplasm. Whereas TorA is induced by both TMAO and dimethylsulfoxide (DMSO), this enzyme has a high substrate specificity and appears to only efficiently reduce TMAO as a natural compound. The structural torA gene encoding the TMAO reductase (TorA) and its flanking regions were amplified using PCR techniques. The torA gene is the third gene of a TMAO-inducible operon (torECAD) encoding the TMAO respiratory components. The torC gene, located upstream from torA encodes a pentahemic c-type cytochrome, likely to be involved in electron transfer to the TorA terminal reductase. TorC was shown to be anchored to the membrane and, like TorA, is induced by TMAO. Except for the TorE protein, which is encoded by the first gene of the torECAD operon, all the tor gene products are homologous to proteins found in the TMAO/DMSO reductase systems from Escherichia coli and Rhodobacter species. In addition, the genetic organization of these systems is similar. Although these bacteria are found in different ecological niches, their respiratory systems appear to be phylogenetically related, suggesting that they come from a common ancestor.     

Female sexual responses in male cats facilitated by olfactory bulbectomy and medial preoptic/anterior hypothalamic lesions.

Using 23 sexually active male cats, the authors performed bilateral lesions of the medial preoptic/anterior hypothalamic area and olfactory bulbectomies, with the order of operations balanced. In all Ss, male sexual behavior was virtually eliminated by the combined operations. Increased levels of female proceptive behavior were seen after either type of lesion alone, and combined operations resulted in increased levels of receptivity. Results support the concept that there exists, within the brains of male animals, the neural basis for the display of female as well as male sexual responses and that certain brain operations may potentiate the display of female responses. However, it does not appear that the reduction of male behavior is necessarily coupled with an increase in female behavior, since no correlation was seen between the degree of enhancement of female behavior and the decrement in male behavior. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synaptic connections between substance P-containing axons and estrogen receptor-synthesizing neurons in the medial preoptic area of the rat brain

Dual-label immunocytochemical procedures were employed to provide ultrastructural evidence for the presence of substance P (SP) in afferents to estrogen-receptive neurons in the medial preoptic area (MPO) of the female rat. SP-immunoreactive axon terminals were observed to innervate the periventricular (PvPO) and medial (MPN) preoptic nuclei of the MPO densely, and to form synaptic connections at these sites with neurons which contain estrogen receptors in their nucleus. These results indicate that estrogen-receptive preoptic neurons may be regulated by SP-containing neuronal pathways via synaptic mechanisms.     

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)     

Changes in dopaminergic neurotransmission do not alter somatic or motivational opiate withdrawal-induced symptoms in rats.

Opiate withdrawal has been correlated with decreased extracellular dopamine (DA) levels in the nucleus accumbens (NAC) of morphine-dependent rats. The authors tested the hypothesis that DA transmission plays a critical role in the induction of motivational and somatic withdrawal symptoms. First, the authors used a 6-hydroxydopamine-induced lesion of the NAC to chronically disrupt mesolimbic DA transmission. Second, global DA neurotransmission was acutely stimulated by the nonselective DA agonist (apomorphine) or inhibited by nonselective DA antagonists (droperidol or flupentixol). Morphine-dependent rats bearing 6-hydroxydopamine-induced lesions displayed naloxone-precipitated motivational and somatic withdrawal symptoms similar to those of sham-lesioned rats. Administration of apomorphine did not reduce naloxone-induced opiate withdrawal. Moreover, in total absence of naloxone, DA antagonists did not precipitate either conditioned place aversion or somatic abstinence signs in dependent rats. Taken together, these findings suggested that DA transmission is not critical for the induction of opiate withdrawal syndrome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microinfusion of cocaine into the medial preoptic area or nucleus accumbens transiently impairs maternal behavior in the rat.

Cocaine was microinfused bilaterally (50 μg/0.5 μl/side) into the medial preoptic area (MPOA) or nucleus accumbens (NA), 2 regions within the rat brain neural circuit known to mediate maternal behavior (MB). Additionally, 2 sites not involved in this neural circuit, the dorsal striatum and dorsal medial hippocampus, were used as control sites. Microinfusion of cocaine into the MPOA or NA impaired MB, whereas infusion into the control sites did not. MB impairment was not temporally coincident with the increased locomotor activity, also documented after cocaine infusion into the MPOA or NA, arguing strongly that impaired MB is a direct, specific effect of cocaine in these areas, not a derivative of increased motor activity. This is the first demonstration that cocaine action on single central nervous system (CNS) sites can impair MB to the same extent as systemic injections. Thus, cocaine's simultaneous effect on multiple CNS sites is not required for MB impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of preoptic, lateral hypothalamic, or dopamine-depleting lesions on behavioral thermoregulation in rats exposed to the cold.

Results of a study with male albino Sprague-Dawley rats indicate that Ss which received medial preoptic/anterior hypothalamic lesions showed impaired physiological thermoregulation in the cold but continued to barpress to activate a heat lamp. After lateral hypothalamic lesions or 6-hydroxydopamine-induced destruction of central dopaminergic neurons, physiological mechansims for body temperature maintenance were unaffected, but performance of the operant task was impaired. In contrast to this difference, Ss from each of the 3 groups constructed nests from tissue paper that were similar in size to one another. These nests generally were much smaller than those of control Ss. The present findings, together with previous observations of behavioral thermoregulation in rats with comparable lesions, are interpreted in terms of the reinforcement obtained by each behavior and the deficits in detecting those reinforcements that may result from each type of brain damage. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lesions of the amygdala, preoptic area, and hypothalamus on estradiol-induced activity in the female rat.

In the 1st of 2 experiments, lesions of the anterior hypothalamic nucleus and the medial preoptic area sharply attenuated enhancement of wheel running by estradiol benzoate (EB) in ovariectomized albino Holtzman rats. 71 Ss received either 3.0 μg EB or oil in daily sc injections. Lesions of the corticomedial amygdala had no effect on wheel running. The hormonal effects on activity were largely independent of any changes in body weight. Exp I indicated that the anterior hypothalamic and medial preoptic areas are critically involved in the induction of activity by estradiol. However, this experiment provided no support for suggestions that the corticomedial amygdala inhibits those structures that mediate the estrogenic induction of activity. In Exp II, food deprivation was used to stimulate activity. Results suggest that the reduction in the ability of estradiol to induce activity following anterior hypothalamic and medial preoptic lesions does not reflect a general inability to become more active. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine infusion does not alter LH levels before or after chronic cocaine exposure in female rhesus monkeys

Cocaine stimulates release of luteinizing hormone (LH) in preclinical and clinical studies but the contribution of the indirect dopamine agonist actions of cocaine to its effects on LH are unclear. In the present study, we examined the effects of exogenous dopamine infusions on LH release in drug-naive, normally cycling, female rhesus monkeys. All studies were conducted during the mid-follicular phase (cycle days 6-8). Three successive 80-min dopamine infusions (10 micrograms/kg/min, intravenous) were alternated with 20- or 40-min interruptions of dopamine infusions. There were no significant changes in LH during or following dopamine infusions. Predopamine baseline LH levels averaged 30 +/- 5.4 ng/ml. LH averaged 31.7 +/- 1.3 ng/ml during dopamine infusions and 31.4 +/- 1.3 ng/ml after dopamine infusions stopped. To determine whether chronic cocaine exposure influenced the effect of dopamine on LH, rhesus females were studied after more than 2 years of cocaine self-administration at an average dose of 6.5 +/- 0.2 mg/kg/day. LH averaged 27.3 +/- 3.3 ng/ml during baseline and 26.9 +/- 0.7 ng/ml and 26.1 +/- 0.7 ng/ml during dopamine infusions and interruptions, respectively. Similarly, during withdrawal from cocaine, baseline LH levels averaged 32.1 +/- 4.5 ng/ml, and LH did not change significantly during dopamine infusions (31.2 +/- 1.1 ng/ml) and infusion interruptions (32.1 +/- 1.1 ng/ml). Under the conditions of the present study, dopamine administration did not change LH levels in gonadally intact rhesus monkeys, and these findings are consistent with previous studies in ovariectomized rhesus females. However, these data are not consistent with clinical reports, and some possible implications of this species difference are discussed. Moreover, these data suggest that the stimulation of LH by cocaine may not be explained by its indirect dopamine agonist actions.     

Preference for mode of obtaining reinforcement in rats with lesions in septal or ventromedial hypothalamic area.

Assigned 54 female Holtzman albino rats to groups receiving sham operations, septal lesions, or ventromedial hypothalamic lesions. In a choice situation where food could be obtained free or by working, lesioned Ss obtained significantly more reinforcement by bar pressing than by not working. This preference for obtaining reinforcement by bar pressing was evident in normal and operated Ss even when different amounts of effort (fixed ratios of l, 3, ll) were required to obtain reinforcement. When adulterated pellets were substituted for regular pellets, operated Ss continued to obtain significantly more reinforcement by bar pressing than normal Ss. Findings indicate the limitation of the explanation that rats with lesions in the ventromedial hypothalamus have reduced appetitive motivation or a general motivational deficit. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ventromedial hypothalamic lesions produced by gold thioglucose do not impair induction of NPY mRNA in the arcuate nucleus by fasting

The motorneuron degeneration (mnd) mutation causes one of the few late-onset progressive neurodegenerations in mice; therefore, the mnd mouse is a valuable paradigm for studying neurodegenerative biology. The mnd mutation may also model human neuronal ceroid lipofuscinosis (NCL) or Batten disease. mnd maps to the centromeric region of mouse chromosome 8, which likely corresponds to portions of human chromosomes 13,8, or 19; we note that the chromosome 13 portion maps close to a region thought to contain the human Type V NCL locus. We have identified candidate genes for the mnd locus from human chromosomes 13,8, and 19, and we are mapping these genes in the mouse to determine their proximity to the mutated locus and to refine the comparative human-mouse map in this area. A candidate gene from human chromosome 13 is LAMP1, which encodes lysosomal membrane protein 1. We found that LAMP1 in the mouse lies within the region of the mnd mutation. Therefore, we sequenced LAMP1 cDNAs from homozygous mnd mice and unrelated wildtype C57BL/6 mice. We find no differences between the two cDNA species in the regions examined, and expression analysis shows a similar LAMP1 protein distribution in wildtype and mutant mice, suggesting that an abnormal accumulation of material within normal lysosome structures is unlikely to be the pathogenetic mechanism in the mnd mouse.     

Motor cortex lesions do not affect learning or performance of the eyeblink response in rabbits.

The possible modulatory role of motor cortex in classical conditioning of the eyeblink response was examined by ablating anterior neocortex in rabbits and training them with an auditory conditioned stimulus (CS) and an airpuff unconditioned stimulus (US) in either a delay (Experiment 1) or a trace (Experiment 2) conditioning paradigm. Topographic measures such as amplitude and onset latency were assessed during conditioning sessions for conditioned responses (CRs) and on separate test days for unconditioned responses (URs) by using a range of US intensities. No lesion effects were observed for learning or performance measures in acquisition or retention of either delay or trace conditioning. During trace conditioning, lesioned rabbits did, however, exhibit a trend toward impairment and demonstrated significantly longer CR latencies. Damage to motor and frontal cortex does not significantly affect eyeblink response performance or learning in either a delay or a trace conditioning paradigm. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine D? receptor stimulation of the nucleus accumbens or the medial preoptic area promotes the onset of maternal behavior in pregnancy-terminated rats.

There is good evidence that interference with the mesolimbic dopamine (DA) system results in impaired maternal responding in postpartum female rats. However, whether activation of the mesolimbic DA system is capable of promoting maternal behavior has not been investigated. This study examined whether increasing DA activity in various brain regions of pregnancy-terminated, naive female rats would stimulate the onset of maternal behavior. Experiments 1 and 2 examined the effects of microinjection of various doses (0, 0.2, or 0.5 μg/0.5 μl/side) of a D? DA receptor agonist, SKF 38393, or a D? DA receptor agonist, quinpirole, into the nucleus accumbens (NA) on latency to show full maternal behavior, and Experiment 3 determined the effects of SKF 38393 injection into a control site. Finally, because the medial preoptic area (MPOA) is also important for maternal behavior, receives DA input, and expresses DA receptors, the authors examined whether microinjection of SKF 38393 into MPOA was capable of stimulating the onset of maternal behavior. Results indicated that microinjection of SKF 38393 into either the NA or the MPOA facilitates maternal responding in pregnancy-terminated rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of D1 or D2 dopamine receptor antagonism in the medial preoptic area, ventral pallidum, or nucleus accumbens on the maternal retrieval response and other aspects of maternal behavior in rats.

The medial preoptic area (MPOA), ventral pallidum (VP), and nucleus accumbens (NA) receive dopaminergic afferents and are involved in maternal behavior. Experiments investigated whether dopamine (DA) receptor antagonism in NA disrupts maternal behavior, determined the type of DA receptor involved, and investigated the involvement of drug spread to VP or MPOA. Injection of SCH 23390 (D1 DA receptor antagonist) into NA of postpartum rats disrupted retrieving at dosage levels that were ineffective when injected into MPOA or VP. Motor impairment was not the cause of the deficit. Injection of eticlopride (D2 DA receptor antagonist) into NA or VP was without effect. Results emphasize the importance of DA action on D1 receptors in NA for retrieval behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)