Abstract
Natural reward and drugs of abuse converge upon the mesolimbic system which mediates motivation and reward behaviors. Drugs induce neural adaptations in this system, including transcriptional, morphological, and synaptic changes, which contribute to the development and expression of drug-related memories and addiction. Previously, it has been reported that sexual experience in male rats, a natural reward behavior, induces similar neuroplasticity in the mesolimbic system and affects natural reward and drug-related behavior. The current study determined whether sexual experience causes long-lasting changes in mating, or ionotropic glutamate receptor trafficking or function in the nucleus accumbens (NAc), following 3 different reward abstinence periods: 1 day, 1 week, or 1 month after final mating session. Male Sprague Dawley rats mated during 5 consecutive days (sexual experience) or remained sexually naïve to serve as controls. Sexually experienced males displayed facilitation of initiation and performance of mating at each time point. Next, intracellular and membrane surface expression of N-methyl-D-aspartate (NMDA: NR1 subunit) and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA: GluA1, GluA2 subunits) receptors in the NAc was determined using a bis(sulfosuccinimidyl)suberate (BS3) protein cross-linking assay followed by Western Blot analysis. NR1 expression was increased at 1 day abstinence both at surface and intracellular, but decreased at surface at 1 week of abstinence. GluA2 was increased intracellularly at 1 week and increased at the surface after 1 month of abstinence. Finally, whole-cell patch clamp electrophysiological recordings determined reduced AMPA/NMDA ratio of synaptic currents in NAc shell neurons following stimulation of cortical afferents in sexually experienced males after all reward abstinence periods. Together, these data show that sexual experience causes long-term alterations in glutamate receptor expression and function in the NAc. Although not identical, this sex experience-induced neuroplasticity has similarities to that caused by psychostimulants, suggesting common mechanisms for reinforcement of natural and drug reward.
Highlights
The mesolimbic system consists of interconnected brain areas, including the ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc) [1]
Sexual experience causes facilitation of subsequent sexual behavior, including increased sexual motivation and performance [23], and influences expression of conditioned place preference for mating [15]. These behavioral changes suggest the occurrence of natural reward-related learning and memory, which is hypothesized to be mediated by alterations in the mesolimbic system induced by mating behavior experience [11]. In support of this hypothesis, we have previously shown that sexual experience caused an upregulation of deltafosB in the NAc, which in turn, was critical for the facilitation of initiation and performance of sexual behavior following sexual experience [23]
Facilitation of sexual behavior was maintained both 1 week and 1 month after last mating session, as latencies to mating parameters were shorter on Test day (1 week or 1 month after day 5 of sexual experience) compared to mating day 1 (Figure 1A: mount latency, 1 month, p = 0.016; Figure 1B: intromission latency, 1 month, p = 0.046; Figure 1C: ejaculation latency, 1 week, p = 0.016; 1 month, p = 0.008) and no significant differences existed between mating day 5 and Test day for any behavioral parameter at any time
Summary
The mesolimbic system consists of interconnected brain areas, including the ventral tegmental area, medial prefrontal cortex (mPFC), and nucleus accumbens (NAc) [1]. Sexual experience causes facilitation of subsequent sexual behavior, including increased sexual motivation and performance [23], and influences expression of conditioned place preference for mating [15] These behavioral changes suggest the occurrence of natural reward-related learning and memory, which is hypothesized to be mediated by alterations in the mesolimbic system induced by mating behavior experience [11]. In support of this hypothesis, we have previously shown that sexual experience caused an upregulation of deltafosB in the NAc, which in turn, was critical for the facilitation of initiation and performance of sexual behavior following sexual experience [23]. Sexual experience and subsequent abstinence from this natural reward cause long-term alterations in the mesolimbic system that are similar to those induced by psychostimulants, and affect behavioral responses to both natural and drug reward
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