Biology subjects

Becker, J. B.

Publications and source records attributed to Becker, J. B..

8 recordsLinked to original sources

bioRxiv2026

Differential acquisition of cocaine and heroin self-administration in a rat model of internalizing versus externalizing temperament

Substance Use Disorders (SUDs) constitute a major and rising public health concern. In addition, there is a growing appreciation that different classes of addictive substances are likely to lead to qualitatively different types of SUDs requiring differing treatment and relapse prevention strategies to be most effectively managed. Biological temperament, particularly on the internalizing - externalizing axis, is well established to influence addiction susceptibility. Externalizing behavior has long been understood to predispose individuals to addiction through novelty-seeking, sensation-seeking and impulsivity, while internalizing behavior provides an alternate pathway into addiction via increased occurrence of comorbid disorders (anxiety, depression). Here, we utilize a selectively bred rat model of internalizing vs externalizing temperament (bred High Responders, representing genetically mediated externalizing behavior and bred Low Responders, representing internalizing behavior) to examine differences in the acquisition of self-administration of the prototypical psychostimulant cocaine and the prototypical opioid heroin (diacetylmorphine). We found that, as predicted, cocaine and heroin drove different patterns of acquisition in the two different bred lines of rats. Further, this was influenced by temperament in complex ways. Notably, in females the "telescoping effect" for opioid addiction-like behavior was primarily specific to externalizing temperament. These findings highlight the impact and interaction of many factors, including drug class, temperament, and sex, on the acquisition of drug-taking behavior. Additionally, these findings indicate that sex differences in addiction vulnerability may be influenced in part by biological temperament.

animal behavior and cognition↗

bioRxiv2025

Effects of Social Housing on Electrically Stimulated Dopamine Release in the Nucleus Accumbens Core and Shell in Female and Male Rats

Dopamine (DA) is a neurotransmitter that is important in the reward system and increased DA release is associated with rewarding properties of drugs. Highly addictive stimulants like methamphetamine (METH) increase DA release and block reuptake, causing the DA to stay in the synapse longer, enhancing its effects. Because the misuse of METH is increasing in the United States, it is important to investigate ways to protect against this highly addictive stimulant. Recent studies have shown that social support can be a protective factor against METH self-administration in females, but not males. Other studies using microdialysis have shown that socially housed females have lower DA release in the nucleus accumbens (NAc) compared to single housed females after treatment with METH. Additionally, researchers have shown that there are sex differences in stimulated DA release. The present study investigates whether social housing affects stimulated DA release after METH treatment. DA release in the NAc core and shell of socially housed and individually housed rats was measured using fast scan cyclic voltammetry (FSCV) with a chronic 16-channel carbon fiber electrode in the NAc. A stimulating electrode was aimed at the ventral tegmental area (VTA) to induce DA release in the NAc. The results showed that social housing enhances electrically stimulated DA release in males and that there was greater DA release in NAc core than shell in single males, but no difference in socially housed males. In females, social housing also enhanced ES DA release. In single females there was greater ES DA release in shell than in core. Additionally, in single housed females there was greater ES DA release over time, while the socially housed females had high ES DA release that remained stable over time. These results suggest that social housing protects females from sensitization, making single females more vulnerable to the addictive properties of METH.

neuroscience↗

bioRxiv2025

Social housing effects of Intermittent Access of Methamphetamine Self-administration and social behavior

Social support is a potentially protective factor against substance use disorders (SUDs). Previous studies in animal models for SUDs have shown that when females are pair housed, they have lower motivation for cocaine and methamphetamine (METH) than females who are single housed. In males, however, social housing has not had the same beneficial effect. This study investigates effects of social housing on METH self-administration in females or males when both cage mates are self-administering METH. The study also investigated how the quality of the relationships changed after METH self-administration. The results show that singly housed females self-administered more METH than socially housed females, while males in both social housing conditions self-administered METH at the same rate. The social behavior data showed that females given saline spent more time apart, however the females given METH spent more time together, suggesting that their social behavior may play a role in the attenuation of METH self-administration. Males social behavior remained unchanged after METH and the dominant male in a pair self-administered more METH than the non-dominant male. Females self-administration was not affected by dominance. The results of this study show that social housing provides some protective benefits to females, but not males, for METH self-administration. Further, the type of relationship between cage mates affects males self-administration and may explain why social housing with a same sex mate is not beneficial for males. STRUCTURED ABSTRACT BackgroundSocial support is a potentially protective factor against substance use disorders (SUDs). Previous studies in rats have shown that when females are pair housed, they have lower motivation for drugs such as cocaine and methamphetamine (METH), than females who are single housed. In males, however, socially housed and singly housed males both have the same motivation for drugs such as cocaine. PurposeThe aim of this study was to investigate if social housing would attenuate METH self-administration in females or males when both cage mates are self-administering METH on an intermittent access schedule (IntA). The study also investigated how the quality of those relationships changed after METH self-administration, if dominance played a role in the rate of self-administration, and the extent to which the quality of the relationships was related to METH self-administration. MethodsMale and female rats were individually housed or housed in same sex pairs from around day 42, then animals underwent self-administration of METH (0.3 mg/kg/inf) on an IntA schedule of reinforcement. Both animals in a pair self-administered METH. Social behavior was evaluated prior to and throughout the period when animals were self-administering METH. ResultsThe results showed that in females, single housed females self-administered more METH than pair housed females, while males in both housing conditions self-administered METH at the same rate. More singly housed females on day one of the IntA had high rates of self-administration, compared to socially housed females. Differences attenuated after the first session, but singly housed females still self-administered METH to a greater extent than pair housed females overall. The social behavior data showed that females given saline spent more time apart while the females given METH spent more time together. This suggested that social behavior may contribute to the attenuation of self-administration in females. Males social behavior largely remained unchanged after METH and males continued to exhibit dominance behaviors. Furthermore, males METH self-administration was affected by dominance, with dominant males exhibiting greater responding for METH than non-dominant males. ConclusionsSocial housing provides some protective benefits to females, but not males, for METH self-administration. Further, the type of relationship between cage mates affects males self-administration and may explain why social housing with a same sex mate is not beneficial for males. HIGHLIGHTSO_LIPair housing in female rats resulted in less methamphetamine self-administration compared with individually housed females. C_LIO_LIPair housing in male rats did not attenuate methamphetamine self-administration compared with single housing. C_LIO_LIFemales self-administering methamphetamine spent more time together. C_LIO_LIMales self-administration of methamphetamine was affected by dominance status. C_LI

neuroscience↗

bioRxiv2025

Sex Specific Attenuation of Reward Preference

Estradiol receptor signaling has a sex-specific impact on the brains reward pathways, enhancing cocaine reinforcement in females but not in males. Selective activation of G-Protein Coupled Estradiol Receptor 1 (GPER-1) in the dorsolateral striatum (DLS) attenuates the reinforcing effects of 0.1% saccharin (SACC) and cocaine in males but not females. This study investigated GPER-1 activation in the DLS and systemically using the GPER-1 agonist, G1, to assess its effect on SACC and cocaine preference in male and female rats. Five experiments were conducted using gonad-intact and gonadectomized animals to determine dose-response effects and the influence of circulating hormones. Intra-DLS GPER-1 activation with 20% G1 selectively reduced SACC preference in intact males but not females, while higher and lower concentrations had no effect. Systemic G1 administration attenuated cocaine-induced conditioned place preference (CPP) in both sexes in a dose-dependent way. Interestingly, systemic administration of G1 did not alter SACC preference in either sex, regardless of the presence or absence of gonadal hormones. These findings suggest that GPER-1 activation influences reward processing in a site, reward, and sex-dependent manner. HighlightsO_LISelective activation of the membrane-associated estradiol receptor, GPER-1, in the dorsolateral striatum (DLS) attenuates preference for a 0.1% saccharin solution (SACC) in male but not female rats. C_LIO_LISystemic activation of the membrane-associated estradiol receptor, GPER-1, attenuates cocaine-induced condition place preference (CPP) in both males and females in a dose-dependent way. C_LIO_LISystemic GPER-1 activation does not influence SACC preference in either sex. C_LI

neuroscience↗

bioRxiv2023

Sex Dependent Regional Differences in Dopamine Release Determined by Chronic Fast-Scan Cyclic Voltammetry in Nucleus Accumbens and Dorsal Striatum

We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation (ES; 60Hz) induced DA release was recorded in the NAc of single or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than in males. Finally, DA release following ES of the medial forebrain bundle at 60Hz was studied over four weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo. Significance StatementDopamine release is not uniform or fixed. In the nucleus accumbens, pair housing, compared with individual housing, is shown to differentially affect dopamine responsiveness to stimulation in a sex-dependent and region-specific way. There are also sex differences in stimulated dopamine release in the dorsolateral striatum of intact rats, which are not seen in gonadectomized rats, indicating the hormone dependence of this sex difference. However, reuptake of dopamine was slower in females than in males, independent of gonadal hormones. Importantly, the electrical stimulation-induced dopamine release in the dorsolateral striatum of gonadectomized rats demonstrated sensitization of dopamine release in vivo within animals for the first time. Thus, stimulated dopamine release exhibits sex-specific neuroplasticity that is modified in females by the housing conditions.

neuroscience↗

bioRxiv2022

Immediate and Long-Term Effects of Tibial Nerve Stimulation on the Sexual Behavior of Female Rats

ObjectivesThere are limited treatment options for female sexual dysfunction (FSD). Percutaneous tibial nerve stimulation (PTNS) has shown improvements in FSD symptoms in neuromodulation clinical studies, but the direct effects on sexual function are not understood. This study evaluated the immediate and long-term effects of PTNS on sexual motivation and receptivity in a rat model of menopausal women. Our primary hypothesis was that long-term PTNS would yield greater changes in sexual behavior than short-term stimulation. Materials and MethodsIn two Experiments, after receiving treatment, we placed ovariectomized female rats in an operant chamber in which the female controls access to a male by nose poking. We used five treatment conditions, which were with or without PTNS and no, partial, or full hormone priming. In Experiment 1, we rotated rats through each condition twice with behavioral testing immediately following treatment for 10 weeks. In Experiment 2, we committed rats to one condition for 6 weeks and tracked sexual behavior over time. We quantified sexual motivation and sexual receptivity with standard measures. ResultsNo primary comparisons were significant in this study. In Experiment 1, we observed increased sexual motivation but not receptivity immediately following PTNS with partial hormone priming, as compared to priming without PTNS. In Experiment 2, we observed trends of increased sexual receptivity and some sexual motivation metrics when PTNS was applied long-term with partial hormone priming, as compared to hormone-primed rats without stimulation. ConclusionsPTNS combined with hormone priming shows potential for increasing sexual motivation in the short-term and sexual receptivity in the long-term in rats. Further studies are needed to examine variability in rat behavior and to investigate PTNS as a treatment for FSD in menopausal women.

neuroscience↗

bioRxiv2019

G-protein coupled estradiol receptor 1 in dorsolateral striatum modulates cocaine preference in male rats

There are sex differences in the response to psychomotor stimulants, where females exhibit a greater response than males, due to the presence of the gonadal hormone estradiol (E2). Extensive research has shown that E2 enhances drug-seeking and the rewarding properties of cocaine for females. The role of E2 in male drug-seeking, however, is not well understood. The current study investigated pharmacological manipulation of E2 receptors in the dorsolateral striatum (DLS) on preference for cocaine in gonad-intact male and female rats. In males, activation of G-protein coupled E2 receptor 1 (GPER1), via administration of ICI 182,780 or G1, attenuated conditioned place preference for 10mg/kg cocaine, while inhibition of GPER1, via G15, enhanced preference at a 5mg/kg cocaine dose. Similarly, GPER1 activation, via G1, prevented males from forming a preference for 0.1% saccharin (SACC) versus plain water. Surprisingly, activation of GPER1 did not alter preference for cocaine or SACC in females. These studies also examined the quantity of E2 receptor mRNA in the dorsal striatum, using qPCR. No sex differences in relative mRNA expression of ER, ER{beta}, and GPER1 were observed. However, there was greater GPER1 mRNA, relative to ER and ER{beta}, in both males and females. The results presented here indicate that E2, acting via GPER1, may be protective against drug preference in male rats.

neuroscience↗

bioRxiv2019

The rodent vaginal microbiome across the estrous cycle and the effect of genital nerve electrical stimulation

Treatment options are limited for the approximately 40% of postmenopausal women worldwide who suffer from female sexual dysfunction (FSD). Neural stimulation has shown potential as a treatment for genital arousal FSD, however the mechanisms for its improvement are unknown. One potential cause of some cases of genital arousal FSD are changes to the composition of the vaginal microbiota, which is associated with vulvovaginal atrophy. The primary hypothesis of this study was that neural stimulation may induce healthy changes in the vaginal microbiome, thereby improving genital arousal FSD symptoms. In this study we used healthy rats, which are a common animal model for sexual function, however the rat vaginal microbiome is understudied. Thus this study also sought to examine the composition of the rat vaginal microbiota. Treatment rats (n=5) received 30 minutes of cutaneous electrical stimulation targeting the genital branch of the pudendal nerve, and Control animals (n=4) had 30-minute sessions without stimulation. Vaginal lavage samples were taken during a 14-day baseline period including multiple estrous periods and after twice-weekly 30-minute sessions across a six-week trial period. Analysis of 16S rRNA gene sequences was used to characterize the rat vaginal microbiota in baseline samples and determine the effect of stimulation. We found that the rat vaginal microbiota is dominated by Proteobacteria, Firmicutes, and Actinobacteria, which changed in relative abundance during the estrous cycle and in relationship to each other. While the overall stimulation effects were unclear in these healthy rats, some Treatment animals had less alteration in microbiota composition between sequential samples than Control animals, suggesting that stimulation may help stabilize the vaginal microbiome. Future studies may consider additional physiological parameters, in addition to the microbiome composition, to further examine vaginal health and the effects of stimulation.

microbiology↗