Conditioning and place-specific sensitization of increases in activity induced by morphine in the VTA

doi:10.1016/0091-3057(84)90018-2

Pharmacology Biochemistry and Behavior

Volume 20, Issue 6, June 1984, Pages 925-934

https://doi.org/10.1016/0091-3057(84)90018-2 Get rights and content

Abstract

The conditionability of increases in locomotor activity induced by morphine administration into the ventral tegmental area was studied in rats. Morphine produced a clear increase in locomotor activity that was reversed by the opiate receptor blocker, naloxone, and blocked by the neuroleptic, pimozide, suggesting the mediation of this effect by the ascending mesolimbic dopamine system. The increase in locomotor activity showed sensitization with repeated morphine administrations and this sensitization was found to be specific to the environment in which morphine was administered. Conditioning tests also revealed that, in the absence of morphine, increased locomotor activity was elicited by the administration environment. Pimozide blocked the development of the conditioned sensitization. These data demonstrate that a learned association developed between this excitatory action of morphine and the administration environment. These results have important implications for the role of conditioning factors in relapse to drug use and may provide an explanation for conditioning data obtained when morphine is administered systemically.

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It has been extensively demonstrated in rodents that repeated morphine treatments produce potent stimulant effects manifested in spontaneous motor activity behavior as hyperactivity (Vezina and Stewart, 1984; Neisewander and Bardo, 1987; Vanderschuren et al., 1999; Powell and Holtzman, 2001; Tzschentke and Schmidt, 1995; Leite Júnior et al., 2019).
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Fig. 6D shows examples of the sections used for counting phosphorylated-ERK-immunoreactive cells in the VTA and NAc following VEH and MOR administration. In line with previous studies (Vezina and Stewart, 1984; Neisewander and Bardo, 1987; Powell and Holtzman, 2001; Lu et al., 2002; Sharf et al., 2010), we found that repeated morphine treatments in rats induced a behavioral locomotor sensitization effect. This effect was context selective in that similar morphine treatments administered unpaired to the test arena did not result in locomotor stimulant effects.
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Conditioning and place-specific sensitization of increases in activity induced by morphine in the VTA

Abstract

Life Sci

Life Sci

Brain Res

Eur J Pharmacol

Br J Pharmacol

Eur J Pharmacol

Eur J Pharmacol

Neuropharmacology

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Brain Res

Neurosci Lett

Eur J Pharmacol

Life Sci

Pharmacol Biochem Behav

Eur J Pharmacol

Life Sci

Behav Biol

Trends Neurosci

Prog Neuropsychopharmacol Biol Psychiatry

Time-dose relationships for locomotor activity effects of morphine after acute or repeated treatment

Br J Pharmacol

Stimulation of dopamine synthesis in caudate nucleus by intrastriatal enkephalins and antagonism by naloxone

Science

The neuroanatomical substrate of opiate reward in the rat

Opiate reward mechanisms mapped by intracranial self-administration

Intracranial self-administration of morphine into various brain regions

Soc Neurosci Abstr

Dissociation of the rewarding and physical dependence-producing properties of morphine

Stimulant effects of enkephalin microinjection into the dopaminergic A10 area

Nature

Differentiation of the dopamine mechanisms mediating accumbens and caudate-putamen

J Pharm Pharmacol

Role of conditioned reinforcers in the initiation, maintenance and extinction of drug-seeking behavior

Pavlov J Biol Sci

Reinstatement of cocaine-reinforced responding in the rat

Psychopharmacology (Berlin)

Drug reinstatement of heroin-reinforced responding in the rat

Psychopharmacology (Berlin)

Conditioning of drug-induced physiological responses

Psychol Rev