Psychomotor activity and cognitive disruption attributable to NMDA, but not sigma, interactions in primates.
We have compared the ability of phencyclidine (PCP)-like or sigma ligands to induce psychomotor effects in primates. In squirrel monkeys, administration of MK-801 (0.001-0.1 mg/kg), PCP (0.03-0.3 mg/kg), (+)-SKF10047 (0.001-3.0 mg/kg) or (-)-SKF10047 (0.1-10 mg/kg) induced ataxia, head weaving and bradykinesia. In contrast, treatment with the selective sigma ligand (+)-pentazocine using doses up to 20 mg/kg failed to induce any overt behaviours. The order of potency for induction of these behaviours was: MK-801 greater than PCP greater than (+)-SKF10047 greater than (-)-SKF10047 much greater than (+)-pentazocine. In rhesus monkeys treatment with MK-801 (0.01-0.04 mg/kg), PCP (0.05-0.2 mg/kg), (+)-SKF10047 (0.75-3.0 mg/kg) or (+)-pentazocine (1-10 mg/kg), disrupted performance of a spatial delayed response task. The potency to induce cognitive disruption was positively correlated with affinity for [3H]MK-801, but not [3H](+)-SKF10047, binding sites in vitro. These findings indicate that the psychomotor and cognitive effects of PCP-like and sigma ligands in primates are mediated through interactions at NMDA, not sigma, receptors.
Boyce
S
S
Merck, Sharpe and Dohme Research Laboratories, Neuroscience Research Center, Harlow, Essex, U.K.
Rupniak
N M
NM
Steventon
M J
MJ
Cook
G
G
Iversen
S D
SD
D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D003071:Cognition / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D017480:Receptors, sigma; D012453:Saimiri; D013028:Space Perception / Q000187:drug effects
D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine; D010423:Pentazocine