, Volume 110, Issue 1–2, pp 119–124 | Cite as

Clozapine's functional mesolimbic selectivity is not duplicated by the addition of anticholinergic action to haloperidol: a brain stimulation study in the rat

  • Eliot L. Gardner
  • Leslie Stern Walker
  • William Paredes
Original Investigations


This study examined whether the anticholinergic potency of the clinically superior antipsychotic drug clozapine contributes to clozapine's anatomically-selective functional inhibition of the mesolimbic dopamine (DA) system, using an electrical brain-stimulation reward (BSR) paradigm in rats that has been previously shown to be highly sensitive to clozapine's mesolimbic functional selectivity. Rats were chronically administered saline, clozapine, haloperidol, or haloperidol plus the anticholinergic compound trihexyphenidyl, and threshold sensitivity of the mesolimbic and nigrostriatal DA systems was assessed using the BSR paradigm, to infer degree of functional DA blockade produced by the chronic drug regimens. Chronic saline produced no change in either DA system. Congruent with previous findings, chronic clozapine powerfully inhibited the mesolimbic DA system but spared the nigrostriatal DA system. Also congruent with previous findings, chronic haloperidol powerfully inhibited both DA systems. Compared to chronic haloperidol alone, chronic haloperidol plus chronic trihexyphenidyl exerted diminished anti-DA action in both the mesolimbic and nigrostriatal DA systems. These results suggest that clozapine's anticholinergic potency is not an adequate explanation for its functional mesolimbic selectivity.

Key words

Clozapine Haloperidol Trihexyphenidyl Dopamine Acetylcholine Mesolimbic Nigrostriatal Antipsychotic Neuroleptic Atypical Schizophrenia Psychosis Substantia nigra Ventral tegmental area Brain stimulation reward Self-stimulation ICSS 


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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Eliot L. Gardner
    • 1
    • 2
  • Leslie Stern Walker
    • 1
  • William Paredes
    • 1
  1. 1.Program in Brain and Behavior, Department of PsychiatryAlbert Einstein College of MedicineBronxUSA
  2. 2.Department of NeuroscienceAlbert Einstein College of MedicineBronxUSA

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