Modulation of morphine sensitization in the rat by contextual stimuli |
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Authors: | A. Badiani M. M. Oates T. E. Robinson |
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Affiliation: | (1) Neuroscience and Biopsychology Programs, The University of Michigan, Ann Arbor, Michigan, USA, US;(2) Department of Pharmacology and Human Physiology, Institute of Medical Pharmacology, University of Rome ”La Sapienza”, 5 Piazzale Aldo Moro, 00185 Rome, Italy e-mail: badiani@uniroma1.it, Fax: +39-06-4991-2497, IT |
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Abstract: | Rationale: The repeated administration of addictive drugs, such as amphetamine, cocaine, and morphine, produces a progressive enhancement (sensitization) of their psychomotor activating effects. We have previously shown that administration of amphetamine or cocaine in a distinct test environment promotes more robust psychomotor sensitization than if they are given at home. No information is available, however, on whether this environmental manipulation has a similar effect on sensitization to morphine, a drug that enhances dopamine (DA) release in the striatum indirectly by disinhibiting midbrain DA neurons. Objectives: The main goal of present study was to determine whether exposure to a distinct environmental context facilitates morphine sensitization. Methods: As an index of psychomotor activation, we used rotational behavior in rats with a uni- lateral 6-hydroxydopamine lesion of the mesostriatal DA system. There are inconsistencies in the literature regarding the ability of morphine to elicit rotational behavior. Therefore, in experiment 1 we determined the effect of 2.0, 3.0, 4.0, 6.0, and 8.0 mg/kg, IP, of morphine on rotational behavior. In experiment 2, we studied the effect of five consecutive IV infusions of saline or morphine (2.0 mg/kg) in rats treated either in their home cage or in a distinct and relatively novel test environment. After 5 days of withdrawal, all rats received an IV infusion of 2.0 mg/kg morphine (Morphine challenge). The following day all rats received an IV infusion of saline (Saline challenge). Results: Morphine produced a dose-dependent increase in rotational behavior. Environmental novelty enhanced both the acute psychomotor response to morphine and its ability to induce psychomotor sensitization. Furthermore, a conditioned rotational response was seen only in animals treated in the novel environment. Conclusions: Environmental novelty can facilitate the development of sensitization to the psychomotor activating effects of major addictive drugs, such as amphetamine, cocaine, and morphine. Received: 29 November 1999 / Accepted: 14 March 2000 |
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Keywords: | Morphine Dopamine 6-OHDA Mesostriatal dopamine system Nucleus accumbens Psychomotor activity Rotational behavior Sensitization Environment Novelty Context Associative learning Conditioning Stress |
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