The effects of
BMY-14802 (5, 10, or 20 mg/kg), a
sigma-receptor ligand showing preclinical evidence of
antipsychotic efficacy, were tested on single-unit activity in the neostriatum of freely moving rats with or without pretreatment with 1.0 mg/kg
D-amphetamine. Relative to resting baseline,
amphetamine activated the large majority of neurons that changed firing rate in close temporal association with movement. All doses of
BMY-14802 reversed this neuronal response, but the effect was most pronounced at 20 mg/kg. This dose, however, was equally likely to reverse or to induce a
haloperidol-like potentiation of those neurons inhibited by
amphetamine. In contrast, 10 mg/kg
BMY-14802 consistently reversed
amphetamine-induced neuronal inhibitions. All doses of
BMY-14802 attenuated the locomotor effects of
amphetamine, but only the higher doses also blocked other aspects of the
amphetamine behavioral response. By itself,
BMY-14802 dose dependently inhibited motor-related neurons, but elicited less behavioral activation than
amphetamine.
BMY-14802 (20 mg/kg) also induced hindlimb
ataxia and occasional backwards locomotion.
Haloperidol (1.0 mg/kg) reliably suppressed both behavior and neuronal activity when injected 30 min after
BMY-14802, whether or not
amphetamine pretreatment was given. Thus,
BMY-14802 shares with other
neuroleptics the capacity to reverse
amphetamine-induced excitations of neostriatal motor-related neurons, whereas other effects of
BMY-14802 reveal some
haloperidol-like actions at 20 mg/kg that do not occur at lower doses.