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Psychopharmacology (Berl). 2000 Aug;151(2-3):273-82.

Modulation of morphine sensitization in the rat by contextual stimuli.

Author information

  • 1Neuroscience and Biopsychology Programs, The University of Michigan, Ann Arbor, USA. badiani@uniroma1.it

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 unilateral 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.

PMID:
10972474
[PubMed - indexed for MEDLINE]
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