DELTA(9)-TETRAHYDROCANNABINOL INCREASES PREFRONTAL CORTICAL CATECHOLAMINERGIC UTILIZATION AND IMPAIRS SPATIAL WORKING-MEMORY IN THE RAT - BLOCKADE OF DOPAMINERGIC EFFECTS WITH HA966

The present study examined Delta(9)-tetrahydrocannabinol (THC)-induced alterations in monoamine transmission in the rat forebrain as well as the effects of the enantiomers of 3-amino-1-hydroxypyrrolid-2-one (HA 966) on the monoamine response to THC. Activation of dopamine (DA) and norepinephrine (NE) but not serotonin (5-HT) turnover in the prefront al cortex (PFC) was observed after THC (5 mg/kg i.p.) administration. Both enantiomers of HA966 completely prevented the effects of THC on P FC DA turnover and partially blocked the THC-induced rise in NE metabo lism. The cognitive consequences of THC exposure were also examined. T HC significantly impaired spatial working, but not reference, memory i n rats, and this effect was ameliorated by HA966. Thus, HA966 prevents the THC-induced increases in PFC DA turnover and impairments of prefr ontal cortical working memory function. Furthermore, these data sugges t that cognitive impairments displayed by marijuana self-administering humans may be related to PFC DA hyperactivity and that HA966 may prev ent this effect. (C) 1997 American College of Neutropsychopharmacology .