Faculty Collaboration Database

The effects of kainic acid lesions on locomotor responses to haloperidol and clozapine. Psychopharmacology (Berl) 1998 Feb;135(3):270-8

Date

03/14/1998

Pubmed ID

9498730

DOI

10.1007/s002130050509

Scopus ID

2-s2.0-0031963466 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Spontaneous and amphetamine-elicited locomotor activity in rats is reduced by most clinically effective antipsychotic drugs. We have recently demonstrated that intracerebroventricular infusion of kainic acid (KA), which produces cell loss in the hippocampus and other limbic-cortical brain regions, increases spontaneous and amphetamine-elicited locomotion. The present study determined if KA lesions alter the suppressive effects of the antipsychotic drugs, haloperidol and clozapine, on spontaneous and amphetamine-elicited locomotor behavior. Young adult male rats (70 days of age) received intracerebroventricular infusions of vehicle or KA, which produced hippocampal pyramidal cell loss in each rat and more variable cell loss or gliosis in the amygdala, piriform cortex, and laterodorsal thalamus. Thirty days post-surgery, lesioned and control rats were tested once a week for locomotor responses to drug treatments. As observed previously, spontaneous locomotor activity and hyperactivity elicited by amphetamine (1.50 mg/kg s.c.) were greater in lesioned animals than controls. In addition, the level of spontaneous activity and/or amphetamine-elicited hyperlocomotion observed in lesioned rats after haloperidol treatment (0.13, 0.35, or 1.50 mg/kg s.c.) was greater than that found in controls. Locomotor responses to low (6.30 mg/kg) and moderate doses of clozapine (20 mg/kg) were similar in lesioned and control rats, although lesioned rats were more active than controls following the administration of a high dose of clozapine (30 mg/kg). These data indicate that the hyperactivity associated with limbic-cortical lesions may be insensitive to reversal by haloperidol, yet uniquely sensitive to suppression by clozapine.

Author List

Bardgett ME, Jackson JL, Taylor BM, Csernansky JG

Author

Jeffrey L. Jackson MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amphetamine
Animals
Antipsychotic Agents
Clozapine
Dopamine Uptake Inhibitors
Excitatory Amino Acid Agonists
Haloperidol
Kainic Acid
Male
Motor Activity
Rats
Rats, Sprague-Dawley