Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide
Groups of rats administered cocaine-HCl (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with (/sup 3/H)DA, modulation of (/sup 3/H)-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in (/sup 3/H)spiperone binding assays. 31 references, 2 figures, 1 table.
- Research Organization:
- Univ. of Colorado Health Sciences Center, Denver
- OSTI ID:
- 5726808
- Journal Information:
- Life Sci.; (United States), Vol. 42:3
- Country of Publication:
- United States
- Language:
- English
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CELL MEMBRANES
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RATS
SPIPERONE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
AMINES
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
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ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
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MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
PSYCHOTROPIC DRUGS
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RODENTS
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques