Chronic cocaine treatment impairs the regulation of synaptosomal 3H-DA release by D2 autoreceptors

Su Jin Yi; Kenneth M. Johnson

doi:10.1016/0091-3057(90)90241-9

Chronic cocaine treatment impairs the regulation of synaptosomal ³H-DA release by D₂ autoreceptors

Su Jin Yi
, Kenneth M. Johnson

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

The effect of repeated administration of cocaine on presynaptic D₂ autoreceptor sensitivity in synaptosomes was studied. In rats treated chronically with saline, the dopamine D₂ agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) caused a significant inhibition of the Ca²⁺-evoked ³H-DA release from synaptosomes prepared from the nucleus accumbens and from the striatum; this effect was blocked by the D₂ antagonist sulpiride. However, chronic cocaine pretreatment abolished the effect of N-0437 in both areas, suggesting a subsensitivity of release-modulating terminal DA autoreceptors. Subsensitive DA autoreceptors would enhance stimulated DA release from mesolimbic and nigrostriatal terminals and may play a role in the behavioral sensitization observed in this paradigm.

Original language	English (US)
Pages (from-to)	457-461
Number of pages	5
Journal	Pharmacology, Biochemistry and Behavior
Volume	36
Issue number	3
DOIs	https://doi.org/10.1016/0091-3057(90)90241-9
State	Published - Jul 1990
Externally published	Yes

Keywords

Behavioral sensitization
Chronic cocaine
DA autoreceptor
DA release

ASJC Scopus subject areas

Biochemistry
Toxicology
Pharmacology
Clinical Biochemistry
Biological Psychiatry
Behavioral Neuroscience

Access to Document

10.1016/0091-3057(90)90241-9

Cite this

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title = "Chronic cocaine treatment impairs the regulation of synaptosomal 3H-DA release by D2 autoreceptors",

abstract = "The effect of repeated administration of cocaine on presynaptic D2 autoreceptor sensitivity in synaptosomes was studied. In rats treated chronically with saline, the dopamine D2 agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) caused a significant inhibition of the Ca2+-evoked 3H-DA release from synaptosomes prepared from the nucleus accumbens and from the striatum; this effect was blocked by the D2 antagonist sulpiride. However, chronic cocaine pretreatment abolished the effect of N-0437 in both areas, suggesting a subsensitivity of release-modulating terminal DA autoreceptors. Subsensitive DA autoreceptors would enhance stimulated DA release from mesolimbic and nigrostriatal terminals and may play a role in the behavioral sensitization observed in this paradigm.",

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AB - The effect of repeated administration of cocaine on presynaptic D2 autoreceptor sensitivity in synaptosomes was studied. In rats treated chronically with saline, the dopamine D2 agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) caused a significant inhibition of the Ca2+-evoked 3H-DA release from synaptosomes prepared from the nucleus accumbens and from the striatum; this effect was blocked by the D2 antagonist sulpiride. However, chronic cocaine pretreatment abolished the effect of N-0437 in both areas, suggesting a subsensitivity of release-modulating terminal DA autoreceptors. Subsensitive DA autoreceptors would enhance stimulated DA release from mesolimbic and nigrostriatal terminals and may play a role in the behavioral sensitization observed in this paradigm.

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