BMY-14802, a sigma ligand and potential antipsychotic drug, reverses amphetamine-induced changes in neostriatal single-unit activity in freely moving rats
✍ Scribed by Zhongrui Wang; John L. Haracz; George V. Rebec
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 905 KB
- Volume
- 12
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
The effects of BMY-14802 (5, 10, or 20 mgkg), 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 m g k g 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 mgkg. This dose, however, was equally likely to reverse or to induce a haloperidollike potentiation of those neurons inhibited by amphetamine. In contrast, 10 m g k g 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 mgkg) also induced hindlimb ataxia and occasional backwards locomotion. Haloperidol (1 .O mgkg) 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 m g k g that do not occur at lower doses.
Behavior, Neostriatum, Sigma receptor o 1992 Wiley-Liss, Inc.