Effects of housing on consummatory successive negative contrast in rats: wire-bottom cages versus polycarbonate tubs

In consummatory successive negative contrast, rats that have had experience drinking 32% sucrose solution drink significantly less 4% sucrose solution than rats that have drunk only 4% solution. This contrast effect occurs reliably when rats are housed in wire-bottom cages, but it occurs significantly less frequently when rats are housed in polycarbonate tubs. Although it is unclear what causes these differences among housing conditions, the present study underscores the impact that housing conditions outside the domain of the training environment can have on behavioral outcomes.     

Ethanol facilitates consummatory extinction

Rats given access to an empty sipper tube after having obtained 32% sucrose in the same situation undergo extinction of consummatory behavior (cE). Ethanol (0.75 and 1 g/kg, i.p.) accelerated cE when administered before the second extinction session. The effect was not attributable to increased activity or state-dependent reduction in consummatory behavior. These data are discussed in the context of research on the effects of ethanol on behavioral assays involving incentive downshifts.     

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats

Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23–28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors.     

Stimulus magnitude effects on the extinction of conditioned consummatory responses to flavored sucrose solution in mice

Paradoxical extinction effects in the conditioned consummatory behavior of rodents have remained largely elusive. Here, appetitive flavor conditioning was studied to determine if a paradoxical magnitude of reinforcement extinction effect (MREE) can occur in the consummatory behavior of mice. During acquisition training of two experiments with factorial design, animals received daily access to either 32% or 4% sucrose solution, and goal tracking time was measured in one-minute bins. In Experiment 1 the solutions were flavored with either 5% or 0.5% almond essence and in Experiment 2 with 2% almond essence, but combined with continuous or partial schedules of reinforcement. During extinction tests of Experiment 1 and 2, water flavored with 0.5% or 2% almond was presented, respectively. Consummatory performance decreased more abruptly during the initial portion of the extinction sessions after training with 32% as compared to 4% sucrose solution. Furthermore, when given a choice test after extinction training (Experiment 2), animals trained with 32% sucrose, preferred the flavored solution, but animals trained with 4% preferred the unflavored solution. These results are interpreted as indicative of the occurrence of a paradoxical MREE in conditioned consummatory behaviors.     

Enhanced anxiety observed in cocaine withdrawn rats is associated with altered reactivity of the dorsomedial prefrontal cortex

Discontinuation of drug intake in cocaine abusers commonly produces a variety of adverse withdrawal symptoms among which anxiety and depression-related behavior are prevailing during the initial period of abstinence. The aim of this study was to provide further insight into the neurobiological dysregulations that might contribute to these pathological states. Rats were treated with cocaine or saline for 14 days (20 mg/kg; i.p) and anxiety-related behavior was assessed in different paradigms (elevated plus-maze (EPM), confinement to an open arm of the EPM and shock-probe burying tests) for up to 4 weeks after withdrawal. Depression-like behavior was assessed by the forced swim test and sucrose preference test. Altogether our results demonstrated that cocaine withdrawal induced persistent heightened levels of anxiety that last for at least 28 days but did not affect depression-like behavior. We then used Fos immunohistochemistry to map neuronal activation patterns in withdrawn rats confined to one open arm of an EPM, and a double labeling procedure using Fos immunohistochemistry and in situ hybridization of glutamic acid decarboxylase or vesicular glutamate transporter mRNAs to identify the phenotype of the activated neurons. Our data showed that the exacerbated anxiety observed in cocaine withdrawn rats exposed to an elevated open arm was accompanied by an altered reactivity of the dorsal part of the medial prefrontal cortex (anterior cingulate and dorsal prelimbic cortices), the paraventricular thalamic nucleus and the lateral and anterior areas of the hypothalamus. In the medial prefrontal cortex, we evidenced a negative correlation between Fos expression in its dorsal part and open arm-induced freezing in NaCl-treated rats but not in cocaine withdrawn rats. We also found that more than 65% of activated neurons were glutamatergic projection neurons. The present study provides new insights into the neuroanatomical regions and neuronal cell types that may underlie pathological anxiety during cocaine withdrawal.     

Different effects of subchronic doses of 17-beta estradiol in two ethologically based models of anxiety utilizing female rats

Estrogen may have differing effects on 'anxiety' responses under different conditions. The current study tested the effects of estrogen on anxiety-like behavior when administered for 6-7 days in ovariectomized (OVX) female rats. Two animal paradigms were utilized; the elevated plus maze (EPM), measuring changes in innate fear of exploration of open spaces; and the social interaction test (SIT), measuring the exploration of a novel, same gender partner. In the EPM, estradiol-treated OVX females both entered and spent more time in the open arms than control OVX females, indicating an anxiolytic-like action of estradiol. In contrast, estradiol treated OVX females interacted less with the partner animal in the SIT compared with controls suggesting anxiogenic-like effects. The possible anxiogenic effect of estradiol in the SIT is supported by two findings: (1) the effect is reversed by the anxiolytic drug alprazolam and (2) estrogen did not affect locomotion and therefore, the reduced social interaction is not due to reduced activity. Acute administration of progesterone (5 mg/kg), which has anxiolytic properties, did not reverse estradiol-induced social interaction deficits, suggesting that lack of progesterone did not account for estradiol's anxiogenic effects. These results, while seemingly contradictory when interpreted within a unified concept of anxiety, may well reflect the ethological roles of reproductive hormones and their effects on different types of exploratory anxiety.     

Neonatal hyperleptinaemia programmes anxiety-like and novelty seeking behaviours but not memory/learning in adult rats

Leptin treatment during lactation programmes for leptin resistance at adulthood, evidenced by hyperleptinaemia, hyperphagia and overweight. Since leptin is known to affect stress response, emotional behaviour and memory/learning performance, the objective of the present study was to evaluate whether neonatal hyperleptinaemia programmes anxiety-like and novelty-seeking behaviours as well as memory/learning in adult male rats. During the first 10 days of lactation (from PN1 to PN10), pups were s.c. injected once per day with either 50 μL of saline (SAL) or murine leptin (LEP — 8 μg/100 g of body mass, saline diluted). Serum leptin was assessed at PN10 and at PN150. Two separate experiments were carried out: 1) experiment one: at PN137, 29 SAL and 30 LEP rats were tested in the elevated plus-maze (EPM) and, at PN142, their behaviour was assessed in the hole board (HB) arena; 2) experiment two: at PN140, a different group of rats consisting of 53 SAL and 56 LEP animals were tested in the radial arm water maze (RAWM). Serum leptin concentration was higher in the LEP group at PN10 and at PN150. LEP animals spent significantly less time in the open arms of the EPM. Furthermore, the number of nose-pokes in the HB arena was higher in LEP rats. There were no differences between groups regarding latency to find the hidden platform in the RAWM. Our results suggests that a central mechanism of leptin resistance at adulthood, caused by neonatal hyperleptinaemia, is associated with an increased level of anxiety and also that it intensifies novelty seeking-behaviour.     

Roux-en-Y gastric bypass in rats increases sucrose taste-related motivated behavior independent of pharmacological GLP-1-receptor modulation

Roux-en-Y gastric bypass (RYGB) surgery has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like peptide-1 receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low-sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief-access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically and while nondeprived postsurgically and 5 h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9-39) (30 μg/kg), agonist exendin-4 (1 μg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01-1.0 M) was presented in 10-s trials. Other rats were tested postsurgically or 15 min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5-3× as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9-39) impacted 0.3 M sucrose intake in a one-bottle test, but never interacted with surgical group to affect brief-access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and in GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model and measure dependent.     

Pre- and postnatal bisphenol A treatment results in persistent deficits in the sexual behavior of male rats, but not female rats, in adulthood

Perinatal administration of the endocrine disruptor bisphenol A (BPA) reportedly inhibits the sexual behavior of sexually naïve adult male rats. In order to evaluate the effects of BPA administration during early development on later reproductive behavior, we administered one of five doses of bisphenol A daily to pregnant female rats throughout gestation and lactation, and quantified the appetitive and consummatory sexual behaviors of the resultant male and female offspring over multiple sexual encounters in adulthood. Males receiving low dose perinatal BPA (50 μg/kg bw/day) showed persistent deficits in sexual behavior in adulthood. Males receiving the highest dose (5 mg/kg bw/day), however, were indistinguishable from controls with respect to consummatory sexual behaviors but showed decreased latencies to engage in those behaviors when sexually naïve, with significant non-linear, or U-shaped, dose-response relationships observed on the first and last day of testing. Adult female sexual behavior was not affected by early BPA administration at any dose tested. These results are consistent with previous reports that BPA exerts behavioral effects especially at low doses, and further indicates that BPA can cause lasting impairment of sexual behavior in males, but does not alter the normal development of female appetitive or consummatory sexual behaviors. To our knowledge, this is the first report indicating that adult sexual performance is impaired in sexually experienced animals following perinatal exposure to bisphenol A.     

Common variations in the pretest environment influence genotypic comparisons in models of anxiety

The behavioral characterization of rodent strains in different studies and laboratories can provide unreplicable results even when genotypes are kept constant and environmental control is maximized. In the present study, the influence of common laboratory environmental variables and their interaction with genotype on the results of behavioral tests of anxiety/emotionality were investigated. To this end, the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which are known to differ for numerous emotionality-related behaviors, were tested in the open field (OF), elevated plus maze (EPM) and black/white box (BWB), while three environmental factors were systematically controlled and analyzed: (1) the experimenter handling the animal (familiar or unfamiliar); (2) the position of the home cage (top or bottom shelf of the rack) and (3) the behavioral state of the animal immediately before the test (arousal or rest). Experimenter familiarity did not alter the behavior of rats in the OF. Cage position, on the other hand, influenced the behavior in the OF and BWB, with rats housed in top cages appearing less anxious than those housed in the bottom. In the BWB (but not in the OF), these effects were genotype dependent. Finally, the behavioral state of the animals prior to testing altered the results of the EPM in a strain-dependent manner, with some anxiety-related genotypic differences being found only among rats that were aroused in their home cages. This study showed that common variations in the laboratory environment interact with genotype in behavioral tests of anxiety/emotionality. Recognizing and understanding such variations can help in the design of more effective experiments.     

The effect of Hoe-427 (an ACTH4-9 analog) on free-choice ethanol consumption in male and female rats.

Ethanol consummatory patterns of individual male and female rats and the effects of Hoe-427 (Ebiratide), an ACTH4-9 analog, thereon, were studied in a test system using 24 hour, two-bottle free choice consumption between 0.2% saccharin and 10% ethanol in 0.2% saccharin. Single, daily i.p. doses (0.03mg/rat) of either ACTH4-10 or its analog resulted in a significant reduction of daily ethanol consumption with no effects on saccharin consumption. After 4 days of treatment, male rats consistently exhibited a rebound increase in ethanol consumption; this effect was not seen in females. The daily ethanol consummatory patterns of the female animals seemed to exhibit a 4-6 day cyclic rhythymicity, suggesting an interaction with estrous cycles. These results support a role for ACTH4-10 in the initiation of ethanol consummatory behavior in rats and suggests the existence of sex differences in this phenomenon.     

Effects of ovine CRF injections into the dorsomedial, dorsolateral and lateral columns of the periaqueductal gray: a functional role for the dorsomedial column

Corticotropin-releasing factor (CRF) and its receptor subtypes have been implicated in the regulation of endocrine, behavioral and autonomic responses to stress, fear and anxiety. Ovine CRF (oCRF) is a nonspecific CRF receptor agonist that produces anxiogenic-like effects when injected locally into the dorsal aspects of the periaqueductal gray (PAG). This structure is subdivided into four distinct longitudinal columns but their exact functional role is not fully understood. The purpose of the present study was to characterize the effects of oCRF (0.25, 0.5 and 1 microg/0.2 microL) injections into the dorsomedial (dmPAG), dorsolateral (dlPAG) and lateral (lPAG) columns of the PAG using an analysis of the exploratory behavior of rats in the elevated plus-maze (EPM) test. The results showed that microinjections of oCRF intra-dmPAG reduced entries and time spent in the open arms and decreased end-arm exploration and head-dipping. In contrast, oCRF intra-dlPAG or lPAG did not affect the exploratory behavior of the animals in the EPM. These findings point to a columnar specificity for the oCRF effects in the PAG, that is, it increased spatial avoidance measures of the EPM test only in the dmPAG. The proaversive effects of oCRF in the dmPAG gain further relevance when combined with previous immunohistochemical studies showing that CRF-containing projections from the periventricular hypothalamic system arch dorsomedially to the PAG, which could function as an important relay station in the midbrain tectum for avoidance behaviors.     

Evidence for a female-specific effect of a chromosome 4 locus on anxiety-related behaviors and ethanol drinking in rats

Previous studies using the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR) led to the mapping of two quantitative trait loci, named Ofil1 (on chromosome 4 of the rat) and Ofil2 (on chromosome 7), for open-field inner locomotion, a behavioral index of anxiety. Studies using other strains showed that the region next to Ofil1 influences measures of not only anxiety but also ethanol consumption. In view of the high prevalence of psychiatric disorders such as anxiety and alcoholism, as well as the comorbidity between them, the present study was designed to better characterize the contribution of these two loci to complex emotional and consummatory responses. Rats deriving from an F2 intercross between the LEW and the SHR strains were selected according to their genotype at markers flanking the loci Ofil1 and Ofil2 and bred to obtain lines of rats homozygous LEW/LEW or SHR/SHR for each of the two loci, thus generating four genotypic combinations. These selected animals as well as purebred LEW and SHR rats of both sexes were submitted to a battery of tests including measures of locomotor activity, anxiety, sweet and bitter taste reinforcement and ethanol intake. Lewis rats displayed more anxiety-like behavior and less ethanol intake than SHR rats. Ofil1 (on chromosome 4) affected both the activity in the center of the open field and ethanol drinking in females only. These results suggest that Ofil1 contains either linked genes with independent influences on anxiety-related responses and ethanol drinking or a pleiotropic gene with simultaneous effects on both traits.     

Trait anxiety affects the orofacial nociceptive response in rats

The aims of the present study were to assess the influence of: a) trait anxiety on orofacial pain; and b) orofacial pain on state anxiety. Forty-four rats were initially exposed to the free-exploratory paradigm for the evaluation of their anxiety profiles. In accordance to the parameter "Percentage of time in the novel side", the animals were considered as presenting high or low levels of trait anxiety when presenting values below the 1st quartile, or above the 3rd quartile, respectively. A week later, formalin-1.5% was injected into the upper lip of each animal. The behavioural nociceptive response, characterized by increased orofacial rubbing (OR), was quantified for 30 minutes, as follows: Total time OR (0-30 minutes: total pain), 1st phase OR (0-6 minutes: neurogenic pain), and 2nd phase OR (12-30 minutes: inflammatory pain). Immediately after this test, but still under the effect of formalin, the rats were submitted to the Elevated Plus-maze test (EPM). The results showed that the high trait anxiety individuals presented higher frequency of OR than the low trait anxiety ones, except during the neurogenic pain period. However, no correlation was found between OR frequency and levels of state anxiety presented on the EPM. In conclusion, the animals presenting higher anxiety profiles were the most susceptible to orofacial pain, nevertheless, orofacial pain did not influence state anxiety.     

Effects of ethanol on locomotor and anxiety-like behaviors and the acquisition of ethanol intake in Lewis and spontaneously hypertensive rats

The purpose of the present study was to investigate whether Lewis (LEW) and spontaneously hypertensive rats (SHR), characterized in numerous behavioral tests as strains with high-anxiety and low-anxiety, respectively, could differ in their sensitivity to the effects of ethanol in the elevated plus maze (EPM) and the open field (OF), two classical models of anxiety/emotionality, as well as in the acquisition of ethanol drinking behavior. It was also of interest to examine the relationship between sweet and bitter fluids preference and ethanol intake. SHR and LEW rats were given saline or ethanol injections (0.6 or 1.2 g/kg, ip.) and tested in the EPM and OF. Subsequently the same animals were given continuous free choice between water and ethanol solution (2-8%). Additional groups of animals were exposed to a free-choice regimen between saccharin (0.002-0.09%) or quinine (0.0001-0.0015%) and water. The low dose of ethanol (0.6 g/kg) induced anxiolytic-like effects and intensive locomotor activation mainly in SHR rats tested in the OF arena. Overall, LEW counterparts were unaffected in OF test. In oral self-administration paradigm, SHR rats consumed significantly more ethanol than LEW rats. Concerning other solutions, SHR rats consumed large amounts of saccharin compared with LEW rats. These data indicate that the SHR preference for ethanol intake may be positively related to their differential sensitivity to the anxiolytic/stimulant effects of ethanol and to the sensitivity of this strain for saccharin reinforcement. In addition, these findings provide evidence that the SHR strain may represent a useful genetic and pharmacological tool to investigate ethanol drinking traits.     

ω-3 多不饱和脂肪酸对PTSD-SPS 大鼠行为学影响的研究

目的:观察饲料中添加ω-3PUFAs对PTSD-SPS大鼠焦虑/抑郁行为的防护作用。方法:将40只健康成年雄性SD大鼠随机分为正常对照组、PTSD-SPS模型组、60%ω-3PUFAs+PTSD-SPS模型组1、60%ω-3PUFAs+PTSD-SPS模型组2。采用高架十字迷宫实验和旷场实验评价实验组大鼠的焦虑/抑郁行为变化。结果:与对照组相比,SPS模型组大鼠进入开放臂的次数比例和时间比例明显减少;中央格停留时间明显缩短(5.56±0.21)s,穿格次数明显减少(30.23±5.96)次,差异均显著(P<0.05)。与SPS模型组相比,60%ω-3PUFAs的SPS组大鼠进入开放臂的次数比例和时间比例明显增加;中央格停留时间明显延长(9.88±1.14)s,穿格次数明显增加(43.22±4.35)次,差异均显著(P<0.05);与对照组相比没有显著差异。结论:膳食补充ω-3多不饱和脂肪酸可以降低PTSD-SPS大鼠焦虑/抑郁程度。     

One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze is not due to acquisition of a phobic avoidance of open arms during initial exposure

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic-like efficacy of benzodiazepines. This phenomenon called one-trial tolerance has been suggested to represent the acquisition of a phobic-like response to the open arms during trial 1. The present study was designed to examine the effects of chlordiazepoxide (5 mg/kg, ip) on the behaviour of rats in a conventional EPM apparatus after previous exposure to a four-open-arm EPM, a four-enclosed arm EPM or a conventional EPM, as well as in naive rats. Chlordiazepoxide had clear-cut anxiolytic-like effects (increased percentage of time spent on the open arms) in a traditional EPM in naive rats and in animals previously exposed to a four-open-arm EPM. However, it was ineffective in rats previously exposed to a traditional or a four-closed-arm EPM. Thus, the phenomenon of one-trial tolerance does not depend upon initial open-arm experience.     

Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats

Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy) on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS ("PRS rats") showed increased anxiety-like behavior in the elevated plus maze (EPM), a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females.     

Alcohol Reward Is Increased after Roux-en-Y Gastric Bypass in Dietary Obese Rats with Differential Effects following Ghrelin Antagonism

Roux-en-Y gastric bypass (RYGB) is one of the most successful treatments for severe obesity and associated comorbidities. One potential adverse outcome, however, is increased risk for alcohol use. As such, we tested whether RYGB alters motivation to self-administer alcohol in outbred dietary obese rats, and investigated the involvement of the ghrelin system as a potential underlying mechanism. High fat (60%kcal from fat) diet-induced obese, non-diabetic male Sprague Dawley rats underwent RYGB (n = 9) or sham operation (Sham, n = 9) and were tested 4 months after surgery on a progressive ratio-10 (PR10) schedule of reinforcement operant task for 2, 4, and 8% ethanol. In addition, the effects of the ghrelin-1a-receptor antagonist D-[Lys3]-GHRP-6 (50, 100 nmol/kg, IP) were tested on PR10 responding for 4% ethanol. Compared to Sham, RYGB rats made significantly more active spout responses to earn reward, more consummatory licks on the ethanol spout, and achieved higher breakpoints. Pretreatment with a single peripheral injection of D-[Lys3]-GHRP-6 at either dose was ineffective in altering appetitive or consummatory responses to 4% ethanol in the Sham group. In contrast, RYGB rats demonstrated reduced operant performance to earn alcohol reward on the test day and reduced consummatory responses for two subsequent days following the drug. Sensitivity to threshold doses of D-[LYS3]-GHRP-6 suggests that an augmented ghrelin system may contribute to increased alcohol reward in RYGB. Further research is warranted to confirm applicability of these findings to humans and to explore ghrelin-receptor targets for treatment of alcohol-related disorders in RYGB patients.     

Reproductive experience modifies the effects of estrogen receptor alpha activity on anxiety-like behavior and corticotropin releasing hormone mRNA expression

Previous studies have demonstrated that prior reproductive experience can influence anxiety-like behaviors, although neural mechanisms underlying this shift remain unknown. Studies in virgin females suggest that activation of the two estrogen receptor subtypes, ERα and ERβ, have differing effects on anxiety. Specifically, ERβ activation has been shown to reduce anxiety-like behaviors, while ERα activation has no significant effect. The purpose of the present study was to examine the possible roles of ERα and ERβ subtypes in parity-induced alterations in anxiety-like behavior, as tested on the elevated plus maze (EPM). Groups of ovariectomized, age-matched, nulliparous and primiparous females were tested on the EPM following administration of the ERα agonist 4,4',4'-(4-Propyl-{1H}-pyrazole-1,3,5-tryl)trisphenol (PPT; 1 mg/kg), the ERβ agonist Diarylpropionitrile (DPN; 1 mg/kg) or vehicle (DMSO). All drugs were administered once daily for 4 days prior to testing as this dosing paradigm has previously been used to demonstrate anxiolytic effects of DPN in virgin rats. In addition, as exposure to the EPM is a psychological stressor, physiological markers of the stress response were measured in both plasma (corticosterone) and brain (corticotropin releasing hormone; CRH) post-EPM testing. Unexpectedly, the ERα agonist PPT selectively increased the time spent exploring the open arms of the EPM in non-lactating, primiparous females, with no significant effects of DPN observed in either nulliparous or primiparous subjects. All females administered PPT and tested on the EPM demonstrated significantly reduced corticosterone secretion when compared to vehicle-treated controls. In addition, significant effects of both reproductive experience and PPT administration on CRH mRNA expression were observed in both the paraventricular nucleus and amygdala using qPCR. These findings indicate that reproductive experience modulates the effects of ERα activation on both EPM behavior related to anxiety and CRH gene expression.