Abstract
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.
Original language | English (US) |
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Pages (from-to) | 119-124 |
Number of pages | 6 |
Journal | Psychopharmacology |
Volume | 110 |
Issue number | 1-2 |
DOIs | |
State | Published - Jan 1993 |
Keywords
- Acetylcholine
- Antipsychotic
- Atypical
- Brain stimulation reward
- Clozapine
- Dopamine
- Haloperidol
- ICSS
- Mesolimbic
- Neuroleptic
- Nigrostriatal
- Psychosis
- Schizophrenia
- Self-stimulation
- Substantia nigra
- Trihexyphenidyl
- Ventral tegmental area
ASJC Scopus subject areas
- Pharmacology