C Dias1, S Lachize, V Boilet, E Huitelec, M Cador. 1. Laboratoire de Neuropsychobiologie des Désadaptations, UMR CRNS 5541, Université Victor Ségalen, Bordeaux 2, 146, rue Leo Saignat, BP 31, 33076 Bordeaux Cedex, France. d_carine@yahoo.fr
Abstract
RATIONALE: The dopaminergic pathways are involved in natural and drug reward related processes. OBJECTIVES: To compare the respective involvement of the dopaminergic receptors D1, D2 and D3 in natural-seeking versus drug-seeking behaviour and evaluate any concomitant expression of locomotor sensitisation. METHODS: In separate experiments, male Wistar rats were trained to self-administer cocaine (0.25 mg/infusion) or to press a lever to obtain food pellets. Following a prolonged period of extinction, reinstatement of lever responding was measured following non-contingent food delivery, cocaine (15 mg/kg), D1-like (SKF 82958, 0.25 mg/kg), D2-like (quinelorane, 0.25 mg/kg) and D3-like (7-OHDPAT, 0.25 mg/kg) agonists. To demonstrate parallel expression of behavioural sensitisation, locomotor activity was recorded during the reinstatement sessions. RESULTS: Cocaine and quinelorane administrations reinstated cocaine-seeking behaviour and induced the expression of locomotor sensitisation, whereas SKF 82958 and 7-OHDPAT had either no effect or non-specific effects. In the food-seeking experiment, we found that quinelorane and 7-OHDPAT did not reinstate lever pressing. Cocaine increased responding on both active and inactive levers, whereas SKF 82958 had a more specific effect with higher responding on the previously food-associated lever. CONCLUSIONS: Our results indicate that expression of locomotor sensitisation and reinstatement of cocaine-seeking but not food-seeking behaviours are in part supported by common dopaminergic substrates, among which the D2 receptors play a crucial role.
RATIONALE: The dopaminergic pathways are involved in natural and drug reward related processes. OBJECTIVES: To compare the respective involvement of the dopaminergic receptors D1, D2 and D3 in natural-seeking versus drug-seeking behaviour and evaluate any concomitant expression of locomotor sensitisation. METHODS: In separate experiments, male Wistar rats were trained to self-administer cocaine (0.25 mg/infusion) or to press a lever to obtain food pellets. Following a prolonged period of extinction, reinstatement of lever responding was measured following non-contingent food delivery, cocaine (15 mg/kg), D1-like (SKF 82958, 0.25 mg/kg), D2-like (quinelorane, 0.25 mg/kg) and D3-like (7-OHDPAT, 0.25 mg/kg) agonists. To demonstrate parallel expression of behavioural sensitisation, locomotor activity was recorded during the reinstatement sessions. RESULTS:Cocaine and quinelorane administrations reinstated cocaine-seeking behaviour and induced the expression of locomotor sensitisation, whereas SKF 82958 and 7-OHDPAT had either no effect or non-specific effects. In the food-seeking experiment, we found that quinelorane and 7-OHDPAT did not reinstate lever pressing. Cocaine increased responding on both active and inactive levers, whereas SKF 82958 had a more specific effect with higher responding on the previously food-associated lever. CONCLUSIONS: Our results indicate that expression of locomotor sensitisation and reinstatement of cocaine-seeking but not food-seeking behaviours are in part supported by common dopaminergic substrates, among which the D2 receptors play a crucial role.
Authors: Laurel M Pritchard; Aaron D Logue; Scott Hayes; Jeffrey A Welge; Ming Xu; Jianhua Zhang; S Paul Berger; Neil M Richtand Journal: Neuropsychopharmacology Date: 2003-01 Impact factor: 7.853