Behavioural pharmacology of the non-competitive 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 [+/-]-5-aminocarbony-10,11-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 metabolism were investigated in rats. Dextrorphan increased locomotor activity but did not induce stereotyped sniffing. ADCI failed to produce any significant motor stimulant and motor depressant actions. Both dextrorphan and ADCI dose-dependently antagonized catalepsy induced by the D-1 dopamine receptor antagonist SCH 23390 or the D-2 dopamine receptor 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 show that dextrorphan and ADCI produce some of the behavioural effects (antagonism of experimentally induced catalepsy) and neurochemical actions (regionally selective stimulation of dopamine metabolism) that have previously been observed in the prototypical non-competitive NMDA antagonist, dizocilpine. The failure of ADCI to induce hyperlocomotion and stereotypy suggests that anticataleptic doses of ADCI may be devoid of the psychotomimetic actions commonly associated with non-competitive blockade of NMDA receptor function.
Bubser
M
M
University of Tübingen, Department of Neuropharmacology, Germany.
Zadow
B
B
Kronthaler
U O
UO
Felsheim
U
U
Rückert
N G
NG
Schmidt
W J
WJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D003917:Dextrorphan / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D001552:Benzazepines; D016194:Receptors, N-Methyl-D-Aspartate; D003917:Dextrorphan; C071316:5-aminocarbonyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine; D016291:Dizocilpine Maleate; D004298:Dopamine