INTRA-VENTRAL TEGMENTAL AREA ADMINISTRATION OF H7 DELAYS, BUT DOES NOT PREVENT THE DEVELOPMENT OF COCAINE-INDUCED SENSITIZATION

Previous studies have suggested that increased protein kinase C activi ty in the ventral tegmental area (VTA) may play a role in the acute an d development of the sensitized behavioral responses to cocaine. The p resent study was conducted to further characterize the role of protein kinases in the development of sensitization. Animals received injecti ons of saline or the nonspecific protein kinase inhibitor H7 into the VTA before each of their four daily systemic injections of saline or c ocaine. Animals were tested for sensitization with a challenge injecti on of systemic cocaine after a withdrawal period of 24 h or 1 week. Te sts for sensitization included monitoring cocaine-induced motor activi ty and/or dopamine concentrations in the nucleus accumbens, as measure d by in vivo microdialysis. Pretreatment with H7 in the VTA attenuated the acute motor stimulant response to cocaine as well as the cocaine- induced increase in extracellular dopamine in the nucleus accumbens. I n addition, the augmented increase in dopamine in the nucleus accumben s of cocaine-sensitized animals was prevented in animals pretreated wi th H7 before each of their daily cocaine injections, when tested after a 24 h withdrawal. However, when tested after a 1 week withdrawal, an imals demonstrated sensitization to both the cocaine-induced increase in motor activity and the cocaine-induced increase in dopamine in the nucleus accumbens regardless of whether they received intra-VTA saline or H7 before each of their daily cocaine injections. These data sugge st that injection of a protein kinase inhibitor into the VTA delays, b ut does not prevent the development of cocaine-induced behavioral sens itization. (C) 1997 Elsevier Science Inc.