Subregion-specific down-regulation of 5-HT3 immunoreactivity in the nucleus accumbens shell during the induction of cocaine sensitization

Repeated exposure to psychostimulants such as cocaine and amphetamine can result in behavioral sensitization, which is believed to model the onset of drug addiction, as well as neural adaptations that occur after repeated drug abuse that lead to addictive behaviors. Dopamine (DA) in the nucleus accumbens (NAc) has been shown to play an integral role in this phenomenon. However, cocaine also acts on the serotonin (5-HT) system, which has been shown to modulate psychostimulant-induced increases in motor behavior and DA release in the NAc. Recently, it has been demonstrated that the shell portion of the NAc can no longer be considered a homogeneous structure and can be subdivided into at least five separate regions. The present study examines 5-HT3 receptors in the subdivisions of the NAc in cocaine-sensitized rats. Rats received a sensitization-inducing regimen of cocaine (twice-daily injections of 15 mg/kg ip for five consecutive days). Two or 14 days following the last injection, rats were given a challenge injection of cocaine (15 mg/kg ip) and sacrificed 2 h later. Sections of the NAc were processed for 5-HT3 immunoreactivity (5-HT3-IR), and the number of puncta was quantified in each of the subregions of the shell, as well as the core of the accumbens. Repeated cocaine administration resulted in robust sensitization that correlated with a transient decrease in the density of 5-HT3 immunoreactive puncta in the intermediate zone of the accumbens shell. After a 2-week withdrawal period, sensitized animals no longer showed any differences in any of the areas examined. These data suggest a possible role for 5-HT3 receptors in the intermediate zone during the induction of cocaine sensitization. (C) 2003 Elsevier Inc. All rights reserved.