Abstract
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 (Δ-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.
Highlights
Brain dopamine is involved in both motivational and consummatory aspects of male sexual behavior
This study shows for the first time that the relative protein levels of markers of neurotropism (BDNF, tyrosine kinase receptor B (trkB)), neuronal activation (∆-FosB), synaptic function and plasticity (Arc and PSA-NCAM; Carta et al, 2018; Serra et al, 2018; Sanna et al, 2019 and references therein) are differentially expressed in the ventral tegmental area (VTA), medial prefrontal cortex (mPFC) and Acb of Dopamine Transporter knockout (DAT KO), HET and wild type (WT) rats, which underwent five copulatory tests and a final session of sexual activity performed during intracerebral microdialysis with a sexually receptive female rat
DAT KO rats needed a lower number of copulatory tests to reach a stable level of sexual activity with a sexually receptive female rat and presented higher levels of sexual activity as indicated by the changes in copulatory parameters across the copulatory tests, mainly shorter latencies to mount, intromit and ejaculate and higher ejaculation frequencies when compared to WT rats
Summary
Brain dopamine is involved in both motivational and consummatory aspects of male sexual behavior. The sexual differences between the two Roman rat lines seem to be related, at least in part, to differences in dopamine function (Sanna et al, 2013, 2014b), in particular in the tone of mesolimbic and mesocortical dopaminergic neurons at the level of the Acb (Sanna et al, 2015b) and of the medial PFC (mPFC; Sanna et al, 2017b) Both naïve (i.e., never exposed before to sexual stimuli) and sexually experienced RHA rats (i.e., exposed to five preliminary copulatory tests), which displayed higher dopamine increases in the Acb and mPFC when exposed to a sexually receptive female rat, displayed higher sexual motivation and better copulatory performances (i.e., higher ejaculation frequency and intromission ratio and shorter post-ejaculatory interval and latencies to mount, intromit and ejaculate) when compared to their RLA counterparts. RHA rats displayed higher levels of C-Fos, ∆-FosB and Arc after sexual activity than their RLA counterparts and these differences were very evident in naïve animals being reduced, not completely, in the experienced ones (Sanna et al, 2019)
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