A comparison of the psychopharmacological profiles of phencyclidine, ketamine and (+) SKF 10,047 in the trimethyltin rat model.
The potential neuroprotective effects of phencyclidine, ketamine and (+) SKF 10,047 were investigated in the trimethyltin (TMT)-treated rat. Of the three drugs used in this study, only phencyclidine (5 mg/kg i.p.) reversed the behavioral hyperactivity and deficits in spatial localization of TMT-treated rats. Neurochemically, phencyclidine and (+) SKF 10,047 were without effect on the neurotransmitters (e.g. noradrenaline, dopamine, serotonin and 5-hydroxindole 3-acetic acid), examined in the amygdaloid cortex and hippocampal regions, while ketamine increased the steady state concentrations of 5-HIAA in the amygdaloid cortex. These results suggest the involvement of the phencyclidine receptor in reversal of the behavioural impairments produced by TMT in rats. The significance of these results with respect to phencyclidine and sigma receptors is discussed. The lack of effect of (+) SKF 10,047 in this model may reflect behavioural differences between phencyclidine and sigma ligands. It may be concluded that the TMT model can be exploited for studying the mechanism of action of molecules liable to have an effect at the phencyclidine receptor site, as opposed to the sigma receptor.
Earley
B
B
Pharmacology Department, University College, Galway, Ireland.
Burke
M
M
Leonard
B E
BE
Gouret
C J
CJ
Junien
J L
JL
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017478:Receptors, Phencyclidine; D013550:Swimming; D014298:Trimethyltin Compounds / Q000633:toxicity*
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D014298:Trimethyltin Compounds; C046488:trimethyltin; D007649:Ketamine; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine