Effect of phencyclidines on hippocampal pyramidal cells.
Phencyclidine (PCP) and several behaviorally active or inactive structural analogs were administered i.v. to urethane-anesthetized rats in order to determine their effects on CA1 pyramidal cell discharges elicited by contralateral CA3 (cCA3) stimulation. PCP and the behaviorally active m-amino derivative (m-NH2 PCP) depressed, in a dose-dependent manner, the amplitude of the population spike evoked in CA1 by a cCA3 stimulation (ED 50s: 0.9 mg/kg for PCP, 0.5 mg/kg for m-NH2 PCP). However, the behaviorally inactive derivatives m-nitro (m-NO2 PCP) and PCP methyliodide (PCP CH3I) were ineffective up to 10 mg/kg. PCP (0.1-0.3 mg/kg i.v.) also decreased the duration of inhibition of CA1 discharges in a paired-stimulus paradigm; this was in contrast to the effects of thiopental and diazepam. In midcollicular-transected, urethane-anesthetized rats, the inhibitory effect of PCP on cCA3-CA1 transmission was not observed but the drug was still as effective as in intact rats in the paired-stimulus paradigm. In animals subjected to 6-hydroxydopamine lesions of the hippocampal noradrenergic innervation (average 85%) decrease in NE content), the potency of PCP in inhibiting cCA3-CA1 transmission was the same as in a group of sham-operated controls. These results suggest the following conclusions: (i) PCP exerts at least 2 separate types of effects in CA1, both of which result from a central action of the drug; (ii) PCP decreases the monosynaptic excitation of CA1 pyramidal cells and this action requires the integrity of brainstem afferents; (iii) PCP may decrease recurrent inhibition or afterhyperpolarization in CA1 via a mechanism which is independent of these connections and, therefore, could result from a direct action of the drug at the level of the hippocampus; (iv) finally, no evidence was found to suggest that the noradrenergic innervation of the hippocampus is critically involved in the action of PCP on CA1 discharges.
D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013874:Thiopental / Q000494:pharmacology
D006892:Hydroxydopamines; D016627:Oxidopamine; D010622:Phencyclidine; D013874:Thiopental; D003975:Diazepam