Dataset Information

Maladaptive Sexual Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex.

ABSTRACT: The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated in male rats that methamphetamine (Meth), when administered concurrently with sexual behavior results in impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience. The present study examined the neural pathways activated during inhibition of sexual behavior in male rats and the effects of concurrent Meth and sexual behavior on neural activity, using ERK phosphorylation (pERK). First, exposure to conditioned aversive stimuli in males trained to inhibit sexual behavior in the CSA paradigm increased pERK expression in medial prefrontal (mPFC), orbitofrontal cortex (OFC) and areas in striatum and amygdala. Second, effects of concurrent Meth and sex experience were tested in males that were exposed to four daily sessions of concurrent Meth (1?mg/kg) or saline and mating and subsequently exposed to CSA one week after last treatment. Meth and mating-treated males showed significant impairment of inhibition of mating, higher pERK expression under baseline conditions, and disrupted pERK induction by exposure to the conditioned aversive stimuli in mPFC and OFC. These alterations of pERK occurred in CaMKII-expressing neurons, suggesting changes in efferent projections of these areas. Altogether, these data show that concurrent Meth and mating experience causes maladapative sexual behavior that is associated with alterations in neural activation in mPFC and OFC.

SUBMITTER: Kuiper LB

PROVIDER: S-EPMC5561340 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Maladaptive Sexual Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex.

Kuiper Lindsey B LB Frohmader Karla S KS Coolen Lique M LM

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20170104 10

The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated in male rats that methamphetamine (Meth), when administered concurrently with sexual behavior results in impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Me ...[more]

PMID: 28051103

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Project description:Central dopamine plays a key role in sexual behavior. Recently, a Dopamine Transporter knockout (DAT KO) rat has been developed, which displays several behavioral dysfunctions that have been related to increased extracellular dopamine levels and altered dopamine turnover secondary to DAT gene silencing. This prompted us to characterize the sexual behavior of these DAT KO rats and their heterozygote (HET) and wild type (WT) counterparts in classical copulatory tests with a sexually receptive female rat and to verify if and how the acquisition of sexual experience changes along five copulatory tests in these rat lines. Extracellular dopamine and glutamic acid concentrations were also measured in the dialysate obtained by intracerebral microdialysis from the nucleus accumbens (Acb) shell of DAT KO, HET and WT rats, which underwent five copulatory tests, when put in the presence of an inaccessible sexually receptive female rat and when copulation was allowed. Markers of neurotropism (BDNF, trkB), neural activation (?-FosB), functional (Arc and PSA-NCAM) and structural synaptic plasticity (synaptophysin, syntaxin-3, PSD-95) were also measured in the ventral tegmental area (VTA), Acb (shell and core) and medial prefrontal cortex (mPFC) by Western Blot assays. The results indicate that the sexual behavior of DAT KO vs. HET and WT rats shows peculiar differences, mainly due to a more rapid acquisition of stable sexual activity levels and to higher levels of sexual motivation and activity. These differences occurred with differential changes in dopamine and glutamic acid concentrations in Acb dialysates during sexual behavior, with lower increases of dopamine and glutamic acid in DAT KO vs. WT and HET rats, and a lower expression of the markers investigated, mainly in the mPFC, in DAT KO vs. WT rats. Together these findings confirm a key role of dopamine in sexual behavior and provide evidence that the permanently high levels of dopamine triggered by DAT gene silencing cause alterations in both the frontocortical glutamatergic neurons projecting to the Acb and VTA and in the mesolimbic dopaminergic neurons, leading to specific brain regional changes in trophic support and neuroplastic processes, which may have a role in the sexual behavior differences found among the three rat genotypes.

Project description:Methamphetamine use disorder (MUD) is a major public health problem worldwide with limited effective treatment options. Previous studies have reported methamphetamine-associated alterations in gut microbiota. A potential role of gut microbiota in regulating methamphetamine-induced brain dysfunction through interactions with the host immune system has been proposed, but evidence for this hypothesis is limited. The present study aimed to investigate the alterations in the fecal microbiota and explore its relationship with systemic inflammation in MUD. Fecal samples were obtained from 26 male subjects with MUD and 17 sex- and age- matched healthy controls. Fecal microbial profiles were analyzed by 16S rRNA sequencing. Plasma inflammatory markers were measured using enzyme-linked immunosorbent assay. Associations between fecal microbiota, systemic inflammatory markers and clinical characteristics were examined by Spearman partial correlation analysis while controlling for possible confounders. Compared with healthy controls, individuals with MUD showed no difference in fecal microbial diversity, but exhibited differences in the relative abundance of several microbial taxa. At the genus level, a higher abundance of Collinsella, Odoribacter and Megasphaera and lower levels of Faecalibacterium, Blautia, Dorea and Streptococcus were detected in subjects with MUD. More importantly, altered fecal microbiota was found to be correlated with plasma levels of CRP, IL-2, IL-6 and IL-10. The order Lactobacillales, exhibiting lower abundance in participants with MUD, was positively related to the duration of methamphetamine abstinence and the plasma level of anti-inflammatory cytokine IL-10. This study is the first to provide evidence for a link between altered fecal microbiota and systemic inflammation in MUD. Further elucidation of interactions between gut microbiota and the host immune system may be beneficial for the development of novel therapeutic approaches for MUD.

Dataset Information

Maladaptive Sexual Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex.

Publications

Maladaptive Sexual Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex.

Similar Datasets

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