Differential effects of sigma and phencyclidine receptor ligands on learning.
Several phencyclidine (PCP) and sigma receptor ligands were examined for their effects on a single trial passive avoidance test in rats. Rats were administered the PCP receptor ligands (+)-5-methyl-10,11-dihydro-5Hdibenzo[a,d]cyclohepten-5,10-im ine maleate (MK-801), PCP, ketamine or the sigma receptor ligands (+)-N-allylnormetazocine ((+)-NANM), (+)-pentazocine, (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP) or 1,3-Di(2-[5-3H]tolyl)guanidine (DTG) subcutaneously prior to acquisition of the passive avoidance response, and tested 24 h later for retention. MK-801 (0.1-0.3 mg/kg), PCP (0.54-1.7 mg/kg), ketamine (10.0-17.2 mg/kg) and (+)-N-allylnormetazocine (5.4-10.0 mg/kg) produced significant memory deficits. (+)-Pentazocine (54 mg/kg) and (+)-3-PPP (30 mg/kg) also produced retention deficits, but at significantly higher doses. DTG (0.3-3.0 mg/kg s.c.) had no effect on retention. There was a positive correlation between production of retention deficits and the compounds' PCP receptor binding affinity. The results suggest that the sigma receptor is not involved in learning the passive avoidance response.
Jones
K W
KW
E.I. du Pont de Nemours and Company, Experimental Station, Wilmington, DE 19880-0400.
Bauerle
L M
LM
DeNoble
V J
VJ
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D007649:Ketamine / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D008568:Memory / Q000187:drug effects*; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010622:Phencyclidine / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000494:pharmacology*; D017478:Receptors, Phencyclidine; D012153:Retention, Psychology / Q000187:drug effects*
D003986:Dibenzocycloheptenes; D008024:Ligands; D010880:Piperidines; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D007649:Ketamine; D016291:Dizocilpine Maleate; C012134:SK&F 10047; C026539:preclamol; D010620:Phenazocine; D010622:Phencyclidine; D010423:Pentazocine