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Chronic molindone treatment: Relative inability to elicit dopamine receptor supersensitivity in rats

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Abstract

Chronic treatment of rats with the antipsychotic drug molindone (2.5 mg/kg) did not elicit behavioral supersensitivity to apomorphine (AP) (0.25 mg/kg) or increased striatal 3H-spiroperidol binding, whereas treatment with haloperidol (0.5–1.0 mg/kg) produced manifestations of dopaminergic supersensitivity in both paradigms. Chronic treatment with a high dose of molindone (20 mg/kg) elicited a small, but significant increase in behavioral sensitivity to AP (57%) which was, however, significantly less than that produced by 1 mg/kg haloperidol (126%, P<0.01). Apparent tolerance to elevation of striatal and frontal cortical 3,4-dihydroxyphenylacetic acid (DOPAC) levels was obtained with chronic molindone treatment (5 or 20 mg/kg). None of the molindone doses used (2.5–50 mg/kg) increased striatal dopamine receptor binding. Scatchard analyses revealed no change in either maximal binding capacity (B max) or dissociation constant (K D). A significant (P<0.001) correlation of receptor binding acitivty and stereotypy score was obtained for haloperidol-, but not molindone-treated rats. These results with molindone in an animal model of tardive dyskinesia suggest that this drug may have a lower potential for eliciting this disorder in humans.

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  1. Millhauser Laboratories, Department of Psychiatry, New York University School of Medicine, 550 First Avenue, 10016, New York, NY, USA

    Emanuel Meller

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  1. Emanuel Meller
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Meller, E. Chronic molindone treatment: Relative inability to elicit dopamine receptor supersensitivity in rats. Psychopharmacology 76, 222–227 (1982). https://doi.org/10.1007/BF00432549

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  • DOI: https://doi.org/10.1007/BF00432549

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