ALTERATIONS IN STRIATAL ACETYLCHOLINE OVERFLOW BY COCAINE, MORPHINE, AND MK-801 - RELATIONSHIP TO LOCOMOTOR OUTPUT

The activity of cholinergic interneurons in the striatum appears to be modulated by a variety of different systems including dopamine, opiat e, and glutamate. The purpose of this study was to characterize the ef fects of drugs known to act on these three systems (i.e., cocaine, mor phine, and MK-801) on striatal ACh overflow with microdialysis procedu res, and to determine if alterations in ACh function induced by these agents are related to changes in locomotor activity. Cocaine was found to increase striatal ACh following intraperitoneal injections of 20 a nd 40 mg/kg, but not 10 mg/kg. The increases in locomotor activity ind uced by cocaine appeared to be dose dependent, while the effects on st riatal ACh were not. Injections of 0.1 mg/kg MK-801 (a non-competitive NMDA receptor antagonist) produced dramatic increases in locomotor ac tivity while decreasing striatal ACh overflow. A lower dose (0.03 mg/k g) of MK-801 failed to alter locomotor activity or striatal ACh. Morph ine produced an apparent dose-dependent elevation in striatal ACh whil e only the lowest dose (5 mg/kg) increased locomotor activity. There a ppears to be no relationship between alterations in striatal ACh and l ocomotor output following systemic administration of these psychoactiv e agents.