Impairing the amphetamine conditioning in rats through the inhibition of hippocampal calcium/calmodulin-dependent protein kinase II activity.

Amphetamine is an addictive drug, possessing reinforcing properties that are believed to be associated with an environmental cue, which resembles a behavioral learning process. This study investigates the role of calcium/calmodulin-dependent protein kinase II (CaM-kinase II) in the acquisition of the amphetamine-produced conditioned place preference (CPP). In Experiment I, rats were trained in an amphetamine-produced (2 mg/kg, i.p.) CPP task. The amphetamine-saline pairing rats spent significantly more time in the box that was associated with the amphetamine injection. Moreover, these rats' hippocampal CaM-kinase II showed significantly higher Ca(2+)-independent activity than that of the controls. In experiment II, the rats received an intra-hippocampal or intra-accumbens injection of specific CaM-kinase II inhibitor (KN-93) or a controlled agent (KN-92) before training in the amphetamine-produced CPP task. The rats receiving the preconditioning intra-hippocampal KN-93 injection showed no amphetamine-produced CPP effect. These results, taken together, indicate that the biological basis of amphetamine-produced place preference behavior might be regulated by the hippocampal CaM-kinase II activity.