Intra-accumbens pertussis toxin sensitizes rats to the locomotor activating effects of a single cocaine challenge.

Drugs of abuse share common neurochemical signaling substrates, many of which are components of the cAMP cascade. Interestingly, a number of these substrates have been linked to drug-influenced behaviors. This study sought to understand the role of one signaling substrate, inhibitory G-proteins, in a drug-induced phenomenon known as behavioral sensitization. Specifically, we used pertussis toxin (PTX) as a tool to investigate the relationship between cocaine-induced alterations in cAMP signaling and behavior. Vehicle (1 micro l/side) or PTX (0.15 or 0.25 micro g/1 micro l/side) was bilaterally infused into the nucleus accumbens of rats. Locomotor activity was assessed on days 7, 14 and 21 post-infusion. Intra-accumbal PTX produced a dose-dependent increase in locomotor activity. On day 21 following behavioral monitoring for 1 h, rats were acutely challenged with cocaine (15 mg/kg, i.p.) and behavioral data were accumulated for an additional 2 h. Intra-accumbal PTX sensitized rats to the locomotor-activating effects of a single cocaine challenge which was dose-dependent. After behavioral testing, brains were removed and processed for in vitro receptor autoradiography using the D(1) receptor ligand [3H] SCH 23390. No changes in D(1) dopamine receptor binding were observed. These findings suggest a role for inhibitory proteins (G(i)/G(o)) within the nucleus acumbens in locomotor activity and also cocaine-induced behavioral sensitization.