Effect of gonadectomy of biochemical indices of striatal dopamine D/sub 1/ and D/sub 2/ receptors, their activity and adaptive response to antipsychotic drug treatment in rat

Thesis/Dissertation · Thu Jan 01 00:00:00 EST 1987

OSTI ID:7183612

Jastrow, T L.R.

Endogenous gonadal steroids in male and female rats were removed by gonadectomy (Gnx). Striatal D/sub 1/ receptors and their activity were characterized by (/sup 3/H)SCH23390 binding parameters and D/sub 1/ receptor-stimulated adenylate cyclase activity in striatal membranes. Striatal D/sub 2/ receptors and their activity were characterized by (/sup 3/H)sulpiride binding parameters in striatal slices and D/sub 2/ receptor-mediated inhibition of forskolin-activated adenylate cyclase activity in striatal membranes. Sub-chronic D/sub 2/ receptor blockade consisted of the administration of the D/sub 2/ specific antagonist sulpiride (20 mg/kg) or vehicle i.p., 2x daily for 21 days followed by a 3 day drug withdrawal period. Gnx of female rats had no affect on striatal D/sub 1/-stimulated adenylate cyclase activity nor on the striatal D/sub 2/ receptor-mediated inhibition of forskolin-activated adenylate cyclase activity. Sub-chronic sulpiride treatment produced no adaptive changes in D/sub 1/-stimulated adenylate cyclase activity in sham-operated or Gnx female rats. Gnx of male rats produced a statistically significant 10% decrease in striatal (/sup 3/H)SCH23390 binding sites with no change in D/sub 1/-stimulated adenylate cyclase activity and no change in striatal(/sup 3/H)sulpiride binding parameters. Sub-chronic sulpiride treatment of sham-operated male rats produced a desensitization of the striatal D/sub 1/-stimulated adenylate cyclase activity with no change in the number of (/sup 3/H)SCH23390 binding sites and no change in (/sup 3/H)sulpiride binding parameters. Gnx of male rats blocked the development of the striatal D/sub 1/ receptor desensitization response elicited by sub-chronic sulpiride treatment, without affecting striatal (/sup 3/H)SCH23390 or (/sup 3/H)sulpiride binding parameters. We have demonstrated that sub-chronic D/sub 2/ receptor blockade in sham-operated male rats results in the desensitization of striatal D/sub 1/ receptor activity.

• Research Organization: Michigan Univ., Ann Arbor (USA)
• OSTI ID: 7183612
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
DOPAMINE
BIOCHEMICAL REACTION KINETICS
RECEPTORS
BIOLOGICAL EFFECTS
CASTRATION
CYCLASES
DRUGS
ENZYME ACTIVITY
GONADS
NUCLEOTIDES
RATS
RESPONSE MODIFYING FACTORS
STEROIDS
SURGERY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARDIOTONICS
CARDIOVASCULAR AGENTS
ENZYMES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LYASES
MAMMALS
MEDICINE
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
REACTION KINETICS
RODENTS
SYMPATHOMIMETICS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques