Varenicline ameliorates nicotine withdrawal-induced learning deficits in C57BL/6 mice.

Varenicline, a partial agonist for α4β2 nicotinic acetylcholine receptors (nAChRs) and full agonist for α7 nAChRs, has been approved for the treatment of smoking cessation. Although recent clinical trials support the efficacy of varenicline for managing global nicotine withdrawal symptoms and for smoking cessation, its effects on animal models of specific withdrawal-associated behaviors have not been tested. The present study evaluated the effects of varenicline on contextual fear conditioning and its effects on nicotine (6.3 mg/kg/day) withdrawal-induced deficits in contextual fear conditioning. Varenicline (0.01, 0.1, 1.0 mg/kg) had no effect on contextual fear conditioning when administered alone, but (0.1 mg/kg) prevented nicotine withdrawal-associated deficits in contextual fear conditioning. These data demonstrate, for the first time, that varenicline reverses nicotine withdrawal-induced deficits in an animal model and suggest that varenicline may be effective at treating nicotine withdrawal-associated deficits in learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The benzodiazepine inverse agonist DMCM as an unconditional stimulus for fear-induced analgesia: Implications for the role of GABAA receptors in fear-related behavior.

When the benzodiazepine inverse agonist DMCM (6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylic acid methyl ester) occupies the benzodiazepine recognition site on the GABAA receptor complex, the inhibitory action of γ-aminobutyric acid (GABA) is attenuated. DMCM acted as an unconditioned stimulus (UCS) for 1 response associated with fear or anxiety, analgesia, as indicated by a dose-dependent (0.25–2.0 mg/kg) suppression of rats' responses to a formalin injection. This was accompanied by other fearlike responses (defecation and urination). The opioid antagonist naltrexone (1.75–24 mg/kg) did not affect these behaviors. Environmental cues associated with DMCM provoked analgesia and defecation in the absence of the drug. The conditional analgesia was reversed by naltrexone (7 mg/kg). DMCM functions as an unconditional fear stimulus by eliciting fear-related behaviors and conditioning those responses to neutral stimuli. The neural circuitry underlying fear conditioning appears to involve tonically inhibitory GABAergic synapses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estradiol and orexin-2 saporin actions on multiple forms of behavioral arousal in female mice.

Estrogens modulate almost all aspects of female behavioral arousal; however, apart from that of sexual behavior, the neurobiology of female arousal remains unclear. Because orexins-hypocretins are neurotransmitters known to be important for behavioral arousal, the authors hypothesized that orexins may be a target for estrogen. Gonadectomized female mice received an intracerebral injection of either phosphate-buffered saline, the neurotoxin saporin (SAP), or the orexin-2-saporin conjugate (OXSAP) in the lateral hypothalamus. SAP- and OXSAP-treated mice were also divided into groups receiving either estradiol capsules or oil capsules. Mice were tested in 3 behavioral tests measuring different modes of arousal: sensory responsiveness, running wheel activity, and fearfulness. OXSAP mice showed decreases in sensory responsiveness and fearfulness concomitant with a reduction in orexin cell number. Estradiol affected all behaviors tested but decreased fearfulness only when combined with OXSAP treatment. These data indicate that estrogens modulate orexins' effects on fearfulness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in mediobasal hypothalamic gonadotropin-releasing hormone messenger ribonucleic acid levels induced by mating or ovariectomy in a reflex ovulator, the ferret

The ferret is a reflex-ovulating species in which receipt of an intromission induces a prolonged (+/- 12 h) preovulatory LH surge in the estrous female. This LH surge is probably stimulated by a large release of GnRH from the mediobasal hypothalamus (MBH). In Exp 1 we asked whether GnRH messenger RNA (mRNA) levels increase in response to mating so as to replenish the MBH GnRH stores needed to sustain the preovulatory LH surge. Estrous females were killed 0, 0.25, 0.5, 1, 3, 6, 14, or 24 h after the onset of a 10-min intromission from a male. Coronal brain sections ranging from the rostral preoptic area caudally to the posterior hypothalamus were processed for in situ hybridization using a 35S-labeled oligoprobe complementary to the human GnRH-coding region. We found no evidence of increased MBH GnRH mRNA levels during the ferret's mating-induced preovulatory LH surge. Instead, the number of GnRH mRNA-expressing cells dropped significantly in the arcuate region beginning 6 h after onset of intromission and remained low thereafter. Furthermore, cellular GnRH mRNA levels decreased in the arcuate region toward the end of the preovulatory LH surge. In Exp 2 we asked whether ovarian hormones regulate MBH GnRH mRNA levels in the female ferret. Ovariectomy of estrous females significantly reduced the number of GnRH mRNA-expressing cells in the arcuate region. This decrease was probably not due to the absence of circulating estradiol. Gonadally intact anestrous females had levels of MBH GnRH mRNA similar to those in estrous females even though plasma estradiol levels were equally low in anestrous females and ovariectomized females. Ovarian hormones other than estradiol may stimulate MBH GnRH mRNA levels in anestrous and estrous females.     

Sex differences and self-report of fear: A psychophysiological assessment.

Hypothesized that, because of differential social learning, females would report fear of spiders more frequently than males would but that males selected for equal self-report of fear would show greater autonomic responsivity than females to slides of spiders. Four groups of 10 undergraduates each (male and female fearful and nonfearful) were assembled. They were told to wait quietly for 10 min, after which they would see slides of tarantulas. Skin conductance level was measured during the anticipatory period and in response to each of the slides. Results confirm the hypothesis that more women would report fear than men but failed to confirm the hypothesis that there would be differential autonomic responding. Fearful Ss, irrespective of sex, showed prolonged autonomic arousal during the entire anticipatory period, whereas nonfearful Ss showed increasing autonomic arousal as the time for the 1st slide presentation approached. This finding is discussed in terms of coping theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of Mitogen-Activated Protein Kinase-Extracellular Signal-Regulated Kinase Disrupts Latent Inhibition of Cued Fear Conditioning in C57BL/6 Mice.

The mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) cascade has been implicated in a variety of associative conditioning tasks. However, the role of the MAPK-ERK cascades in modulating conditioning is less clear. The authors examined the effect of the potent and selective MAPK-ERK inhibitor SL327 on latent inhibition of cued fear conditioning. The results demonstrate that 50 mg/kg and 100 mg/kg SL327 disrupt latent inhibition of cued fear conditioning. These data provide evidence for an essential role of the MAPK-ERK cascade in tasks that modulate the strength of associative conditioning. The results are discussed in relation to the molecular mechanisms that support latent inhibition of cued fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nicotine Enhances Contextual Fear Conditioning and Ameliorates Ethanol-Induced Deficits in Contextual Fear Conditioning.

Nicotine and ethanol are 2 commonly used and abused drugs that have divergent effects on learning. The present study examined the effects of acute nicotine (0.25 mg/kg), ethanol (1.0 g/kg), and ethanol-nicotine coadministration on fear conditioning in C57BL/6 mice. Mice were assessed for contextual and cued fear conditioning at 1 day and 1 week posttraining. Ethanol disrupted acquisition but not consolidation of contextual fear conditioning; nicotine enhanced contextual fear conditioning and ameliorated ethanol-associated deficits in contextual fear conditioning. Mecamylamine antagonized this effect. Fear conditioning was reassessed 1 week after initial testing with no drug administered. At the 1-week retest, mice previously treated with nicotine continued to show enhanced contextual fear, and mice previously treated with ethanol continued to show contextual fear deficits. Thus, nicotine both produces a long-lasting enhancement of contextual fear conditioning and protects against ethanol-associated deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal androgens time neuroendocrine puberty in the sheep: effect of testosterone dose

In sheep, prenatal exposure to androgens during a critical period for sexual differentiation of the brain (30-90 days of gestation; 145 days is term) can advance the timing of puberty in females and prevent the preovulatory LH surge. The present study tests the hypothesis that in sheep, the timing of neuroendocrine sexual maturation is related to the amount of prenatal steroid exposure. In addition, we determined if different steroid requirements exist for sexual differentiation of the tonic and surge modes of gonadotropin secretion. Testosterone was administered weekly to three groups of pregnant ewes from days 30-90 of gestation at doses of 200, 80, or 32 mg/week. The resulting androgenized female lambs together with control males and females (n = 5-7/group) were gonadectomized at 3 weeks of age, and gonadal steroids were replaced with a SILASTIC brand estradiol-filled capsule. LH concentrations were measured from biweekly blood samples. Sustained increases in circulating LH were considered to reflect the initiation of neuroendocrine puberty. In male lambs, LH secretion started to increase at 8.3 +/- 0.9 weeks of age (mean +/- SEM). The two highest doses of prenatal androgen advanced the onset of neuroendocrine sexual maturation in females. In the 200 mg androgenized females, the pubertal LH rise (10.2 +/- 2.0 weeks) began about the same time as in males. In the 80 mg treatment group, LH concentrations increased at 16.2 +/- 1.5 weeks, which was later than in males, but well before that in normal females (27.1 +/- 0.7 weeks). For females treated with the lowest dose of androgen (32 mg), the pubertal LH increase (24.6 +/- 1.9 weeks) began about the same time as in normal females. To test the function of the LH surge system, LH was measured every 2 h for 60 h after an acute increase in circulating estradiol was produced by implanting additional estrogen capsules. All control females produced a surge in response to acute estradiol stimulation. LH surges did not occur in males, 200 mg androgenized females, or 80 mg androgenized females. Of six females from the 32 mg treatment group, two produced LH surges in response to the stimulatory feedback action of estradiol. We conclude that the greater the amount of prenatal testosterone, the earlier the initiation of the pubertal LH rise. Moreover, the finding that low doses of testosterone (32 mg/week) are capable of abolishing the LH surge without significantly advancing the timing of puberty supports our hypothesis that different steroid requirements exist for sexual differentiation of tonic and surge modes of LH secretion.     

Isolation reduces contextual but not auditory-cue fear conditioning: A role for endogenous opioids.

Isolation for several hours after fear conditioning reduces contextual but not auditory-cue fear conditioning (J. W. Rudy, 1996). This isolation effect is reversed by both centrally and peripherally acting opioid receptor antagonists. As in isolation, systemically administered morphine given immediately after conditioning also reduces contextual fear conditioning. Morphine's effect is also reversed by both centrally and peripherally acting opioid receptor antagonists. Exposure to the conditioning context has been shown to eliminate the effect of isolation on contextual fear conditioning (J. W. Rudy, 1996). Context preexposure also eliminated the effect of morphine on contextual fear conditioning. These results imply that opioids released in the periphery play an important role in producing the isolation effect and that they do so by disrupting the postconditioning memory consolidation processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modafinil and memory: Effects of modafinil on Morris water maze learning and Pavlovian fear conditioning.

Modafinil has been shown to promote wakefulness and some studies suggest the drug can improve cognitive function. Because of many similarities, the mechanism of action may be comparable to classical psychostimulants, although the exact mechanisms of modafinil's actions in wakefulness and cognitive enhancement are unknown. The current study aims to further examine the effects of modafinil as a cognitive enhancer on hippocampus-dependent memory in mice. A high dose of modafinil (75 mg/kg ip) given before training improved acquisition on a Morris water maze. When given only before testing, modafinil did not affect water maze performance. We also examined modafinil (0.075 to 75 mg/kg) on Pavlovian fear conditioning. A low dose of pretraining modafinil (0.75 mg/kg) enhanced memory of contextual fear conditioning (tested off-drug 1 week later) whereas a high dose (75 mg/kg) disrupted memory. Pretraining modafinil did not affect cued conditioning at any dose tested, and immediate posttraining modafinil had no effect on either cued or contextual fear. These results suggest that modafinil's effects of memory are more selective than amphetamine or cocaine and specific to hippocampus-dependent memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

From lynching to gay bashing: the elusive connection between economic conditions and hate crime

Two experiments (n = 48 and n = 45) investigated the effects of caffeine-induced arousal on differential classical conditioning of eyeblink (experiment 1) and autonomic (experiment 2) responses. Three groups of human subjects received double-blind administration of 0, 2, and 4 mg/kg oral caffeine (groups 0, 2, and 4, respectively). Twenty minutes after caffeine administration, a differential classical conditioning procedure was in effect. Physiological and subjective arousal was assessed by readings of blood pressure, skin conductance level, and a questionnaire, administered before caffeine administration, and after the conditioning procedure. The results showed increased indexes of physiological arousal in groups 2 and 4. In experiment 1, differential classical eyeblink conditioning was observed in groups 0 and 4, whereas no differential conditioning was seen in group 2. In experiment 2, differential classical conditioning was seen in group 0, whereas caffeine-induced arousal masked acquisition of conditioned skin conductance responses in group 4. This group displayed increased resistance to extinction compared to the other groups. Group 2, which had an intermediate level of arousal, did not display differential conditioning in either experiment. Taken together, the results indicate that small increases in arousal may be detrimental to learning, and larger increases in arousal may reverse this effect.     

Neurochemical basis of conditioned partner preference in the female rat: II. Disruption by flupenthixol.

The effects of the dopamine receptor antagonist flupenthixol were examined on the development of conditioned partner preference induced by paced copulation in female rats. In Experiment 1, ovariectomized, hormone-primed rats were conditioned to associate scented and unscented males with paced and nonpaced copulation, respectively. Females in Experiment 2 associated albino or pigmented males with paced or nonpaced copulation. Flupenthixol or saline was administered before each conditioning trial. During a final drug-free preference test, females could choose to copulate with either a pacing-related or nonpacing-related male. Saline-trained females copulated preferentially with the pacing-related male, whereas flupenthixol disrupted odor but not strain conditioning. The role of dopamine in conditioned partner preference depends on the type of stimuli to be learned. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Same-sex and opposite-sex best friend interactions among high school juniors and seniors

Eighteen adolescents were videotaped during same-sex and opposite-sex interactions in the eleventh and twelfth grades. In both grades, females felt more comfortable during same-sex interactions than during opposite-sex interactions, and they rated their same-sex partners more positively than did males. Females in both grades and males in eleventh grade showed more peer intimacy than did males in twelfth grade. Eleventh-grade females showed the most playful behaviors (the most engaged state). More synchrony (matching of behavior) was found for the animated state in the twelfth grade as compared with the eleventh grade.     

Morphine amplifies norepinephrine (NE)-induced LH release but blocks NE-stimulated increases in LHRH mRNA levels: comparison of responses obtained in ovariectomized, estrogen-treated normal and androgen-sterilized rats

In these studies we examined the temporal effects of intracerebroventricular (i.c.v.) infusions of norepinephrine (NE) on plasma LH and on LHRH mRNA levels in the organum vasculosum of the lamina terminalis (OVLT) and in neurons located in the rostral (r), middle (m) and caudal (c) preoptic areas (POA) of ovariectomized, estrogen-treated rats. Thereafter, we compared these responses to those which occur in androgen-sterilized rats (ASR). NE infusions not only increased plasma LH concentrations but within 1 h after NE, LHRH mRNA levels also were increased significantly in the OVLT and rPOA but not in the mPOA or cPOA. By 4 h, these message levels still were elevated in the OVLT and rPOA and they now also were significantly higher than control values in the mPOA and cPOA. While NE also increased LH secretion in ASR, the plasma LH concentrations obtained were markedly blunted compared to control values. Moreover, NE infusions did not alter single cell levels of LHRH mRNA in any region of the rostral hypothalamus. Previously, we have reported that morphine (s.c.) markedly amplifies NE-induced LH release and questioned whether these responses are accompanied by concomitant augmented increases in LHRH mRNA levels. Morphine alone did not affect basal LHRH mRNA or plasma LH levels. However, when rats were pretreated with morphine (-15 min) and NE was infused i.c.v. at 0 time, significant amplification of LH release occurred but, unexpectedly, morphine completely blocked NE-induced increases in LHRH mRNA levels in all of the neurons we examined. Morphine also amplified LH release in ASR but these responses were significantly less than those obtained in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exon scrambling of MLL transcripts occur commonly and mimic partial genomic duplication of the gene

The aim of this study was to test the hypothesis that prolactin may up- and down-regulate prolactin receptor gene expression in the anterior pituitary gland and hypothalamus respectively. Experiments were carried out in bantams (Gallus domesticus). Comparisons were made of concentrations of PRLR mRNA in the anterior pituitary gland and basal and preoptic hypothalamus in adult males and females held on long days (low vs high plasma prolactin); in 3-week-old juvenile male and females on short days (high vs low plasma prolactin); in 8-week-old juvenile male and females on short days (both low plasma prolactin); in adult laying, incubating, and out-of-lay (high, very high, and low plasma prolactin, respectively); in adult cockerels exposed to long or short days (high vs low prolactin); and in adult hens exposed to long or short days (high vs low prolactin). There was a sex difference in anterior pituitary and basal hypothalamic PRLR mRNA, with lower values in both tissues in females than in males. Compared with laying and out-of-lay hens, anterior pituitary and basal hypothalamic PRLR mRNA concentrations in incubating hens were increased and decreased, respectively. In adult birds of either sex held on long or short days, there was no difference in pituitary PRLR mRNA, while basal hypothalamic PRLR mRNA was lower on short days. PRLR mRNA in the preoptic hypothalamus was not affected by sex, reproductive state, or photoperiod. It is concluded that there is no consistent relationship between plasma prolactin, in the physiological range, and the concentration of PRLR mRNA in the anterior pituitary gland, basal hypothalamus, and preoptic hypothalamus.     

Binding of low mobility group proteins with DNA examined in homologous and heterologous systems by gel retardation assay

In addition to age-related deficits in morphine antinociception in female rats, gender and gonadectomy differences have also been observed, with male rats displaying greater magnitudes of effects than females and castrated males. Since there are little data indicating how aging, gender, and gonadectomy interact in modulating morphine antinociception, the present study evaluated alterations in this response as functions of age (6, 12, 18, and 24 months), gender, and gonadal status (intact, gonadectomized) across a dose range (1-10 mg/kg) and time course (0.5-2 h) on the tail-flick test. The maximal percentage effect (MPE) of morphine (1 mg/kg) was significantly increased in castrated males (18 months), sham females (18 and 24 months), and ovariectomized females (18 months) relative to 6-month-old groups. Increases in the MPE of morphine (1 mg/kg) occurred in sham females (24 months) relative to corresponding sham males and ovariectomized females. The MPE of morphine (2.5 mg/kg) was significantly increased in sham males (18 months) and decreased in sham females (12 months). Decreases in the MPE of morphine (2.5 mg/kg) occurred in castrated males (18 and 24 months) as well as sham (18 months) and ovariectomized (18 and 24 months) females relative to sham males. Whereas the MPE of morphine (5 mg/kg) was unchanged by these variables, the MPE of morphine (10 mg/kg) was significantly decreased in sham females (18 and 24 months) relative to females aged 6 months, as well as males and ovariectomized females aged 24 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of trace amounts of albumin in human bronchoalveolar lavage fluids by fluorometry with chromazurol S

Effects of altered gonadotropin and prolactin (PRL) secretion on luteinizing hormone (LH), PRL and their testicular receptors (R) were studied in neonatal and adult rats. Changes in gene expression were monitored by measurements of steady-state mRNA levels. Five-day and 90-day-old male rats received a single s.c. injection of hCG (600 IU/kg), 1 mg/kg bromocriptine (BR) twice daily, or their combination. After 2 or 8 days, the responses of LH, PRL, their testicular R, and testosterone (T) were assessed, including measurements of the appropriate mRNA levels. Vehicle-treated age-matched animals served as controls. hCG suppressed serum LH in 2 days in adult rats from 0.85 +/- 0.16 to 0.04 +/- 0.01 microg/l, and in neonates from 0.59 +/- 0.29 to levels below 0.01 microg/l (p < 0.01 for both). This was accompanied at both ages by a 60% decrease in pituitary content of the LH beta-subunit mRNA (p < 0.01), but a decrease in the alpha-chain (40%, p < 0.05) occurred only in neonates. hCG increased serum PRL in adult rats in 8 days over 2-fold (p < 0.01); this did not occur in neonates. In neonates, BR increased the LH subunit mRNAs 2-fold in 8 days (p < 0.01) without a concomitant effect on serum LH; no BR effects on the LH parameters were seen in adult animals. BR decreased pituitary PRL protein and mRNA levels at both ages (p < 0.01-0.05), but serum PRL decreased only in the adults. The homologous down-regulation of testicular LHR (near 100%) was accompanied in adults by a 30% decrease in LHR mRNA (p < 0.05). Also BR at this age decreased LHR binding (75% in 8 days, p < 0.01), but in this case no change occurred in the cognate mRNA. hCG and BR slightly up-regulated in adults PRLR binding, but only the 2-day effect of BR was accompanied by a 60% increase in PRLR mRNA (p < 0.05). In neonates, both hCG and BR increased testicular LHR and PRLR mRNA levels (p < 0.01-0.05). In adult animals, both hCG and BR suppressed testicular and serum T levels after 8 days (40-70%, p < 0.01-0.05); only BR was inhibitory to T by 8 days in the neonates (p < 0.05). In conclusion, the homologous and heterologous regulatory effects of hCG and BR on LH, PRL and their testicular R levels were only partly explained by changes in steady-state levels of the respective mRNAs. In general, the autoregulatory effects on LHR and PRLR appeared to affect steady-state levels of cognate mRNAs, whereas heteroregulation predominately involved changes at the protein level. The responses of the neonatal pituitary-gonadal axis to hCG and/or BR differed greatly from those observed in the adult, indicating that the mechanisms involved in these regulatory events in adult animals are a result of gradual postnatal development.     

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.     

The dithiocarbamate fungicide thiram disrupts the hormonal control of ovulation in the female rat

Thiram has been reported to inhibit dopamine-beta-hydroxylase (D beta H), thereby affecting norepinephrine (NE) synthesis. Because NE is a neurotransmitter that is known to play an important role in the hypothalamic regulation of pituitary function, the acute effects of the thiram on the hormonal control of ovulation in the rat were investigated. Ovariectomized, estrogen-primed female rats were given a single injection of thiram (0, 6, 12, 25, 50, and 100 mg/kg, i.p.) at 1100 h and serum LH was measured in serial bleeds. Thiram at 100 and 50 mg/kg completely blocked the LH surge in all rats tested, while 12 and 25 mg/kg blocked the surge in 40 and 75% of the treated animals, respectively. Six mg/kg had no effect. Ovulation was then assessed in intact, proestrous females in response to thiram administration (0, 12, 25, or 50 mg/kg) at 0900, 1100, 1300, or 1800 h. Ovulation was blocked by 25 and 50 mg/kg at 1300 h in all rats, but when injected at 1100 h only the 50 mg/kg dose was effective. No such blockade was found with 50 mg/kg injected at 0900 and 1800 h. To assess the influence of thiram on the LH surge in intact rats, additional females were dosed at 1300 h on the day of proestrus and blood collected over that same day. Thiram at 50 mg/kg blocked the LH surge in all rats, while 25 mg/kg blocked the surge in 60% of the females tested. No effect occurred with 12 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex differences in the daily rhythm of vasoactive intestinal polypeptide but not arginine vasopressin messenger ribonucleic acid in the suprachiasmatic nuclei

The timing of the preovulatory surge of LH in female rodents is tightly coupled to the environmental light/dark cycle. This coupling is mediated by the circadian pacemaker located in the suprachiasmatic nuclei (SCN). Studies indicate that vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), which are synthesized in the SCN, transmit circadian information from the SCN to GnRH neurons, thereby regulating the timing of the LH surge. However, to date, the rhythmic expression of these two peptides in the SCN has only been examined in males. The pattern of VIP expression in males is difficult to reconcile with its role in the LH surge. The purpose of the present study was to assess the rhythm of VIP messenger RNA (mRNA) levels in the SCN of female rats under several endocrine conditions. We compared this rhythm to that in males and to AVP mRNA rhythms in all experimental groups. In all groups of females, VIP mRNA levels were rhythmic, with peak expression occurring during the light phase and a nadir occurring during the dark phase. The rhythm was approximately 12 h out of phase compared with that in males. The rhythmic expression of AVP mRNA in the SCN was virtually identical in all groups of animals. Based on these results, we conclude that 1) the rhythm of VIP seen in the SCN of females during the day may serve as a facilitory signal from the SCN to GnRH neurons; 2) the sex-specific pattern of VIP mRNA does not depend on estradiol; and 3) AVP gene expression within the SCN is not sexually differentiated or altered by estradiol.