Identification of neural circuits controlling male sexual behavior and sexual motivation by manganese-enhanced magnetic resonance imaging.

Introduction: Different techniques have been used to identify the brain regions that control sexual motivation and sexual behavior. However, the influence of sexual experience on the activation of these brain regions in the same subject is unknown. Using manganese-enhanced magnetic resonance imaging (MEMRI), we analyzed the activation of brain regions in the sexual incentive motivation (SIM) and the partner preference PP (tests) on weeks 1, 5, and 10 in male rats tested for 10 weeks. AIM. In experiment 1, we analyzed the possible toxic effects of 16 mg/kg of MnCl2 on male sexual behavior, running wheel, and motor execution. In experiment 2, subjects were tested for SIM and PP using MEMRI. Methods: In both experiments, a dose of 16 mg/kg (s.c) of chloride manganese (MnCl2) was administered 24 h before subjects were tested and placed immediately thereafter in a 7-Tesla Bruker scanner. Results: In experiment 1, the dose of 16 mg/kg of MnCl2 did not induce behavioral alterations that could interfere with interpreting the imaging data. In experiment 2, we found a clear preference for the female in both the SIM and PP tests. We found a higher signal intensity in the olfactory bulb (OB) in week 1 of the SIM test compared to the control group. We also found increased signal intensity in the socio-sexual behavior and mesolimbic reward circuits in the SIM test in week 1. In the PP test, we found a higher signal intensity in the ventral tegmental area (VTA) in week 10 compared to the control group. In the same test, we found increased signal intensity in the socio-sexual and mesolimbic reward circuits in week 5 compared to the control group. Cohen's d analysis of the whole brain revealed that as the subjects gained sexual experience we observed a higher brain activation in the OB in the SIM group. The PP group showed higher brain activation in the cortex and subcortical structures as they acquired sexual experience. Discussion: As the subjects gain sexual experience, more structures of the reward and socio-sexual circuits are recruited, resulting in different, and large brain activations.

Brain circuits activated by female sexual behavior evaluated by manganese enhanced magnetic resonance imaging.

Magnetic resonance imaging (MRI) allows obtaining anatomical and functional information of the brain in the same subject at different times. Manganese-enhanced MRI (MEMRI) uses manganese ions to identify brain activity, although in high doses it might produce neurotoxic effects. Our aims were to identify a manganese dose that does not affect motivated behaviors such as sexual behavior, running wheel and the rotarod test. The second goal was to determine the optimal dose of chloride manganese (MnCl2) that will allow us to evaluate activation of brain regions after females mated controlling (pacing) the sexual interaction. To achieve that, two experiments were performed. In experiment 1 we evaluated the effects of two doses of MnCl2, 8 and 16 mg/kg. Subjects were injected with one of the doses of MnCl2 24 hours before the test on sessions 1, 5 and 10 and immediately thereafter scanned. Female sexual behavior, running wheel and the rotarod were evaluated once a week for 10 weeks. In experiment 2 we followed a similar procedure, but females paced the sexual interaction once a week for 10 weeks and were injected with one of the doses of MnCl2 24 hours before the test and immediately thereafter scanned on sessions 1, 5 and 10. The results of experiment 1 show that neither dose of MnCl2 induces alterations on sexual behavior, running wheel and rotarod. Experiment 2 demonstrated that MEMRI allow us to detect activation of different brain regions after sexual behavior, including the olfactory bulb (OB), the bed nucleus of the stria terminalis (BNST), the amygdala (AMG), the medial preoptic area (MPOA), the ventromedial hypothalamus (VMH), the nucleus accumbens (NAcc), the striatum (STR) and the hippocampus (Hipp) allowing the identification of changes in brain circuits activated by sexual behavior. The socio sexual circuit showed a higher signal intensity on session 5 than the reward circuit and the control groups indicating that even with sexual experience the activation of the reward circuit requires the activation of the socio sexual circuit. Our study demonstrates that MEMRI can be used repeatedly in the same subject to evaluate the activation of brain circuits after motivated behaviors and how can this activation change with experience.