title: Neurotensin-deficient mice show altered responses to antipsychotic drugs.
abstract: The peptide transmitter neurotensin (NT) exerts diverse neurochemical effects that resemble those seen after acute administration of antipsychotic drugs (APDs). These drugs also induce NT expression in the striatum; this and other convergent findings have led to the suggestion that NT may mediate some APD effects. Here, we demonstrate that the ability of the typical APD haloperidol to induce Fos expression in the dorsolateral striatum is markedly attenuated in NT-null mutant mice. The induction of Fos and NT in the dorsolateral striatum in response to typical, but not atypical, APDs has led to the hypothesis that the increased expression of these proteins is mechanistically related to the production of extrapyramidal side effects (EPS). However, we found that catalepsy, which is thought to reflect the EPS of typical APDs, is unaffected in NT-null mutant mice, suggesting that NT does not contribute to the generation of EPS. We conclude that NT is required for haloperidol-elicited activation of a specific population of striatal neurons but not haloperidol-induced catalepsy. These results are consistent with the hypothesis that endogenous NT mediates a specific subset of APD actions.
authors: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA. paul.dobner@umassmed.edu
authors: P R
authors: PR
authors: Dobner
authors: J
authors: J
authors: Fadel
authors: N
authors: N
authors: Deitemeyer
authors: R E
authors: RE
authors: Carraway
authors: A Y
authors: AY
authors: Deutch
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D017353:Gene Deletion; D018390:Gene Targeting; D006220:Haloperidol / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000502:physiology*
chemical_list: D014150:Antipsychotic Agents; D009496:Neurotensin; D006220:Haloperidol