BEHAVIORAL PHARMACOLOGY OF THE NONCOMPETITIVE NMDA ANTAGONISTS DEXTRORPHAN AND ADCI - RELATIONS BETWEEN LOCOMOTOR STIMULATION, ANTICATALEPTIC POTENTIAL AND FOREBRAIN DOPAMINE METABOLISM

The effects of systemic administration of the non-competitive N-methyl -D-aspartate (NMDA) antagonists dextrorphan (10-40 mg/kg, i.p.) and 0, 11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (ADCI) (25-70 mg/kg, i.p.) on basal ganglia-mediated behaviour and on forebrain dopamine me tabolism were investigated in rats. Dextrorphan increased locomotor ac tivity but did not induce stereotyped sniffing. ADCI failed to produce any significant motor stimulant and motor depressant actions. Both de xtrorphan and ADCI dose-dependently antagonized catalepsy induced by t he D-1 dopamine receptor antagonist SCH 23390 or the D-2 dopamine rece ptor antagonist haloperidol. Only the highest doses of dextrorphan and ADCI increased dopamine metabolism in the prefrontal cortex and/or in the nucleus accumbens, but not in the dorsal striatum. Our results sh ow that dextrorphan and ADCI produce some of the behavioural effects ( antagonism of experimentally induced catalepsy) and neurochemical acti ons (regionally selective stimulation of dopamine metabolism) that hav e previously been observed in the prototypical non-competitive NMDA an tagonist, dizocilpine. The failure of ADCI to induce hyperlocomotion a nd stereotypy suggests that anticataleptic doses of ADCI may be devoid of the psychotomimetic actions commonly associated with non-competiti ve blockade of NMDA receptor function.