Abstract
Rationale: Combining neuroleptics with 5-HT(1A) ligands is thought to improve the preclinical profile of neuroleptics and may be of interest in the development of new compounds that have greater therapeutic potential and/or are better tolerated. Objective: To examine 1) the ability of 5-HT(1A) ligands to alter the effects of neuroleptics in preclinical models for antipsychotic potential (hindlimb retraction time in the paw test) and extrapyramidal side-effects (forelimb retraction time in the paw test; catalepsy tests), 2) the role of intrinsic activity at 5-HT(1A) receptors in the modulatory effects of 5-HT(1A) ligands, and 3) the generality of the interactions across neuroleptics. Methods: The effects of different doses of 5-HT(1A) ligands with intrinsic activity ranging from high (e.g., 8-OH-DPAT) to low (e.g., WAY 100135) administered together with a fixed, high dose of the neuroleptics haloperidol, risperidone, and tropapride were examined in the paw test and on catalepsy. Results: Firstly, the 5-HT(1A) agonists 8-OH- DPAT and ipsapirone attenuated the extrapyramidal-like effects of haloperidol and risperidone more than their therapeutic-like effects; this was not observed for tropapride, where all of its effects were markedly attenuated. Secondly, neither the weak 5-HT(1A) agonist WAY 100135 nor the silent antagonist WAY 100635 attenuated the effects of neuroleptics. Thirdly, neuroleptics apparently differed in their sensitivity to interactions with 5- HT(1A) agonists inasmuch as 8-OH-DPAT and ipsapirone attenuated the effects of tropapride on hindlimb retraction times more than those of haloperidol or risperidone. Conclusions: The present data suggest that 5-HT(1A) agonists with intermediate or high, but not low, intrinsic activity may abolish the extrapyramidal effects of neuroleptics. Together with results of previous studies, it appears that 5-HT(1A) agonists alter the antipsychotic-like effects of neuroleptics, although this may depend on the neuroleptic studied.
Original language | English (US) |
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Pages (from-to) | 20-29 |
Number of pages | 10 |
Journal | Psychopharmacology |
Volume | 144 |
Issue number | 1 |
DOIs | |
State | Published - Jun 3 1999 |
Externally published | Yes |
Keywords
- Antipsychotic
- Catalepsy
- Dopamine D receptor
- Extrapyramidal side- effect
- Intrinsic activity
- Neuroleptic
- Paw test
- Rat
- Schizophrenia
- Serotonin 5-HT(1A) receptor
ASJC Scopus subject areas
- Pharmacology