CHANGES OF BEHAVIOR AND MONOAMINE METABOLITES IN THE RAT-BRAIN AFTER REPEATED METHAMPHETAMINE ADMINISTRATION - EFFECTS OF DURATION OF REPEATED ADMINISTRATION

1. The authors studied the mechanism of the reverse-tolerance phenomen on caused by long-term administration of central stimulant drugs. Meth amphetamine(MAP) was chronically administered to rats, and the reverse -tolerance phenomenon was studied in terms of behavioral changes and c hanges in monoamine metabolites, the latter being examined by in vivo microdialysis of the extracellular compartment of the corpus striatum. The authors also studied [H-3]SCH23390 and [H-3]spiperone binding to striatal membranes after chronic MAP administration. 2. MAP(4 mg/kg) o r saline was administered intraperitoneally once daily to male rats. I n Groups 1 and 2, 10 and 30 injections of MAP were given, respectively . In Groups 3 and 4, animals received 10 and 30 injections of saline a s controls. One week after the final injection, all rats were challeng ed with 4 mg/kg MAP. 3. Groups 1 and 2 displayed more intense stereoty py than Groups 3 and 4, indicating that behavioral sensitization had b een achieved in the former. Dopamine(DA) levels increased rapidly in r esponse to MAP challenge in all groups, with the increases in Groups 1 and 2 being more marked than that in Groups 3 and 4. Group 1 showed g reater persistence and a higher rate of DA increase than Group 2. 4. T he number of D-1 and D-2 dopamine receptors did not change after the r epeated MAP administration. 5. The rate of increase in DA release indu ced by MAP was dependent on the duration of repeated administration, a nd there was no correlation between the intensity of stereotypy and th e rate of increase in DA release induced by MAP. These findings sugges t that enhancement in DA release is unlikely to be the sole cause of b ehavioral sensitization.