Repeated stimulation of L-type calcium channels in the rat ventral tegmental area mimics the initiation of behavioral sensitization to cocaine

Abstract.

Rationale: A substantial body of evidence indicates that ion flux through L-type calcium channels and N-methyl-d-aspartate (NMDA) receptors contributes to behavioral sensitization to cocaine. Objectives: The following experiments were designed to evaluate the role of calcium influx through L-type calcium channels or NMDA receptors in the ventral tegmental area (VTA) in the initiation of behavioral sensitization to cocaine. Methods: The L-type calcium channel agonist BayK 8644, the glutamate agonist NMDA, or vehicle was microinjected into the VTA on 3 consecutive days. Following a 2-week withdrawal period, all rats received a challenge injection of cocaine (15 mg/kg, i.p.) in order to assess potential cross-sensitization with the NMDA or BayK 8644 pretreatments. Results: Repeated intra-VTA microinjections of BayK 8644, but not NMDA, resulted in an augmentation of the behavioral response to cocaine. Conclusions: These results indicate that calcium influx through L-type calcium channels produces neurophysiological adaptations that mimic those resulting from intermittent exposure to cocaine.