title: Clozapine pre-treatment has a protracted hypolocomotor effect on the induction and expression of amphetamine sensitization.
abstract: Amphetamine locomotor sensitization is an animal model for the study of addiction and schizophrenia. The antipsychotic clozapine blocks the hyperlocomotion induced by an acute injection of amphetamine, but its effect on locomotor sensitization after repeated amphetamine administration remains unknown. In the present study we investigate the effect of repeated administration of clozapine on the induction and expression of amphetamine locomotor sensitization. We propose that repeated administration of clozapine blocks the induction and expression of amphetamine sensitization. Male Sprague-Dawley rats were classified according to their locomotor response to an acute saline injection in high responder saline (HRS) or low responder saline (LRS). Rats from both groups were injected once daily with amphetamine for 5 consecutive days. Horizontal locomotor activity was measured during 40 min. Four days after the last injection, an acute dose of amphetamine was administered to assess the expression of sensitization. Clozapine was injected once daily for 4 consecutive days before (pre-treatment) or after (treatment) induction of sensitization. Pre-treatment with clozapine significantly decreases both acute amphetamine-induced hyperlocomotion and the induction and expression of amphetamine sensitization only in LRS rats, showing a protracted hypolocomotor effect. On the other hand, clozapine treatment had no effect over locomotor response on the expression of amphetamine sensitization in either LRS or HRS rats. These data suggest that clozapine effect on amphetamine locomotor response depends on individual differences. Also, our results suggest that clozapine pre-treatment attenuates the neuroplasticity underlying amphetamine sensitization, but clozapine treatment is unable to reverse these changes once amphetamine sensitization has been induced.
authors: Department of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago, Chile; Millennium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Andrea Susana
authors: AS
authors: Herrera
authors: José Patricio
authors: JP
authors: Casanova
authors: Rafael Ignacio
authors: RI
authors: Gatica
authors: Fabiola
authors: F
authors: Escobar
authors: José Antonio
authors: JA
authors: Fuentealba
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003024:Clozapine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D000661:Amphetamine; D003024:Clozapine
keywords: ANOVA; Amphetamine; Clozapine; DA; HR; HRS; LR; LRS; Locomotor sensitization; NAc; PCP; SUD; VTA; analysis of variance; dopamine; high responder; high responder saline; i.p; intraperitoneal; low responder; low responder saline; mPFC; medial prefrontal cortex; nucleus accumbens; phenylciclidine; substance use disorder; ventral tegmental area