Neurochemical correlates of cross-sensitization between repeated d-amphetamine administration and male rat sexual behavior.

摘要

Behavioral sensitization due to repeated and intermittent administration of psychostimulants, such as cocaine and d-amphetamine, is accompanied by enhanced function in limbic-motor circuitry that is involved in the generation of motivated behavior. The present experiments investigated the effect of sensitization, induced by repeated injections of d-amphetamine, on sexual behavior in the naive male rat tested in a drug-free state. It was hypothesized that prior d-amphetamine treatment would facilitate male rat sexual behavior.; Injections of either d-amphetamine (1.5 mg/kg, IP) or saline were given every other day for a total of 10 injections, and this regimen induced behavioral sensitization of locomotor activity in drug-treated male rats. After a three-week post-drug period, d-amphetamine-treated rats exhibited facilitated sexual behavior as indicated by shorter latencies to mount and intromit, as well as a general increase in the amount of copulation. Furthermore, sensitized rats displayed a facilitated acquisition of sexual behavior (i.e., mount and intromission latency 300s for three consecutive days). After repeated sexual experience, rats pre-treated with d-amphetamine also showed an augmented increase in appetitive locomotor activity (i.e., level changes) made in anticipation of the presentation of a receptive female. In a separate experiment, enhanced sexual behavior was observed to be independent of the environment in which repeated administration of d-amphetamine occurred, indicating that facilitation was not a consequence of conditioned associations between drug and test environment.; In a final microdialysis experiment, there was an augmented efflux of dopamine (DA) in the nucleus accumbens (NAC) of d-amphetamine-sensitized rats compared to non-sensitized control rats when a receptive female was present behind a screen (35% vs 17%). Although there was a significant increase in NAC DA concentrations from baseline in both sensitized and non-sensitized rats during copulation, there was a greater increase in DA efflux in the NAC of sensitized rats during the first 10-min copulatory sample (60% vs 37%).; These results demonstrate that behavioral sensitization due to repeated psychostimulant administration can "cross-sensitize" to a natural behavior, such as sex, and that increased NAC DA release may contribute to the facilitation of appetitive and consummatory aspects of this behavior. Furthermore, the subsequent facilitation of anticipatory sexual behavior (i.e., level changes) after repeated experience in rats previously treated with d-amphetamine, suggests that behavioral sensitization can influence incentive learning.