Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(88)90634-0· OSTI ID:5726808

Dwoskin, L P; Peris, J; Yasuda, R P; Philpott, K; Zahniser, N R

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), Journal Name: Life Sci.; (United States) Vol. 42:3; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALOIDS
AMINES
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COCAINE
DOPAMINE
DRUGS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
PSYCHOTROPIC DRUGS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SENSITIVITY
SPIPERONE
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES