Dopamine, Noradrenaline and Differences in Sexual Behavior between Roman High and Low Avoidance Male Rats: A Microdialysis Study in the Medial Prefrontal Cortex

Abstract

Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the mesolimbic dopaminergic system of RHA rats vs. RLA rats, revealed by the higher increase of dopamine found in the dialysate obtained from the nucleus accumbens of RHA than RLA rats during sexual activity. This work shows that extracellular dopamine and noradrenaline (NA) also, increase in the dialysate from the medial prefrontal cortex (mPFC) of male RHA and RLA rats put in the presence of an inaccessible female rat and more markedly during direct sexual interaction. Such increases in dopamine (and its main metabolite 3,4-dihydroxyphenylacetic acid, DOPAC) and NA were found in both sexually naïve and experienced animals, but they were higher: (i) in RHA than in RLA rats; and (ii) in sexually experienced RHA and RLA rats than in their naïve counterparts. Finally, the differences in dopamine and NA in the mPFC occurred concomitantly to those in sexual activity, as RHA rats displayed higher levels of sexual motivation and copulatory performance than RLA rats in both the sexually naïve and experienced conditions. These results suggest that a higher dopaminergic tone also occurs in the mPFC, together with an increased noradrenergic tone, which may be involved in the different copulatory patterns found in RHA and RLA rats, as suggested for the mesolimbic dopaminergic system.

Own or dam’s genotype? Classical colony breeding may bias spontaneous and stress‐challenged activity in DAT‐mutant rats

“…Estrous cycle was monitored in all rats as previously described (Sanna et al, ). The overall period for locomotor activity evaluation was reduced to 49 days, from which we extracted seven complete cycles with 4 days each.…”

Altered Sexual Behavior in Dopamine Transporter (DAT) Knockout Male Rats: A Behavioral, Neurochemical and Intracerebral Microdialysis Study

“…On the day of the experiment, during the dark phase of the cycle, the rats were transferred to a mating cage (45 cm × 30 cm × 24 cm) located in a soundproof room lit by a dim red light. The mating cage contained another small Plexiglas cage (15 cm × 15 cm × 15 cm) with 25 holes (Ø 2 mm) in each vertical wall to allow for visual, olfactory and acoustic communication (Sanna et al, 2015b(Sanna et al, , 2017b. After a 2 h habituation period, the microdialysis probe was connected via polyethylene tubing to a CMA/100 microinfusion pump (Harvard Apparatus, Holliston, MA, USA) and perfused with Ringer's solution, containing 147 mM NaCl, 3 mM KCl and 1.2 mM CaCl 2 , pH 6.5, at a constant flow rate of 2.5 µl/min.…”

“…Thirty minutes after the introduction of the female rat, the small cage was removed from the mating cage and sexual interaction/copulation allowed for 60 min, during which four more dialysate aliquots were collected and sexual parameters recorded (see above). After 60 min of copulation, the female rat was removed from the mating cage and one additional dialysate aliquot collected (Pfaus and Everitt, 1995;Melis et al, 2003;Sanna et al, 2015bSanna et al, , 2017b.…”

“…Dopamine concentration in the dialysate from the Acb shell was measured by high-pressure liquid chromatography (HPLC) on a 7.5 cm × 3.0 mm i.d., Supelcosil C18, 3 µm particle size column (Supelco, Supelchem, Milan, Italy) coupled to electrochemical detection (Coulochem II, ESA, Cambridge, MA, USA) using a 4011 dual cell, as already described (Sanna et al, 2015b(Sanna et al, , 2017b. Detection was performed in reduction mode with potentials set to +350 and -180 mV.…”

“…For instance, we have recently reported (Sanna et al, 2014a) significant differences in both motivational and performance aspects of sexual behavior between Roman High-and Low-Avoidance (RHA and RLA) rats, which are two lines of rats psychogenetically selected for their extremely divergent acquisition of the active avoidance response in the shuttle box, and which display opposite biobehavioral traits (Giorgi et al, 2007(Giorgi et al, , 2019. 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(Sanna et al, , 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). Accordingly, 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 also 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.…”