Specific effects by the psychotomimetic drugsd-amphetamine and phencyclidine on the performance of an aversely motivated successive visual discrimination in the rat.

Rats were trained to perform a conditioned avoidance response to white noise in a conventional two-compartment "shuttle-box". The partition between the compartments had two openings, however, and the correct passage (leftor right) was signalled by changes in background illumination. In this situation the psychotomimetic compoundsd-amphetamine (4 mg kg(-1) IP) and phencyclidine (PCP) (2 mg kg(-1) SC) were found to selectively disrupt the visual discrimination. Thed-amphetamine-induced abnormal behavior in this situation has previously been linked to excessive dopamine (DA) receptor stimulation, not controlled by nerve impulse flow and its regulation by important local feed-back mechanisms. Thus, the psychotomimetic effects produced by this compound should not only by due to increased DA receptor activationper se, but also to a disruption of normal patterns of firing and release in dopaminergic neurons. There is evidence to suggest that PCP via an excitatory amino acid (EAA) receptor produces a similar net effect on brain meso-limbic dopaminergic neurotransmission via an increased rate of firing, accompanied by regularization of firing (loss of burst activity). In support for a mediation of PCP-induced effects via EAA receptors, the local application of kynurenic acid into the ventral forebrain (4.7µg, bilaterally) was found also to produce a selective disruption of discriminative performance. It should be noted, however, thatd-amphetamine-induced loss of discriminative behavior, but not that induced by PCP, was antagonized by haloperidol (0.1-0.2 mg kg(-1) IP) administration. It is thus possible that at least some effects of PCP in this situation are mediated on the efferent side of the dopaminergic neuron. It is suggested that the abnormal behavior, as evidenced by a loss of discriminative (but not avoidance) behavior, is due to disruption of normal, feed-back regulated, nerve impulse flow.