Effects of acute amphetamine (AMPH) treatment on rat striatal dopamine (DA) receptor activity
Upon administration of AMPH rats display a complex series of dose and time dependent behaviors and changes in dopaminergic activity. They found a decrease in D1 DA receptor-stimulated adenylate cyclase (DA-AC) activity in rat striatal membranes after acute in vivo AMPH at a dose and time of intense stereotyped behavior. The Ka for D1-AC activity increased and the Vmax decreased in striatal membranes from rats given 7.5 mg/kg AMPH i.p. and killed 1 hr later as compared to saline (SAL) controls. They examined whether the decrease of DA-AC was due to a change in receptor number or activation of GTP-binding protein, Ns. Female Holtzman rats were injected with SAL or 7.5 mg/kg AMPH and killed 1 hr later. A 27,000 x g striatal particulate fraction was prepared for AC assay or (/sup 3/H)DA binding with 10 nM spiroperidol. They found no difference in stimulation of AC by NaF, GTP or GppNHp at any dose tested in membranes from SAL- and AMPH-treated rats. Calmodulin-stimulated AC was also unchanged after AMPH. Specific binding at a saturating concentration of (/sup 3/H)DA was 191 +/- 31 and 117 +/- 14 fmol/mg prot in membranes from SAL- and AMPH-treated rats, respectively. This suggests an alteration is occurring at the level of the D1 receptor rather than at coupling of Ns with the AC catalytic subunit.
- Research Organization:
- Univ. of Michigan, Ann Arbor
- OSTI ID:
- 6933057
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMPHETAMINES
BIOLOGICAL EFFECTS
CYCLASES
ENZYME ACTIVITY
DOPAMINE
BIOCHEMICAL REACTION KINETICS
RECEPTORS
CELL MEMBRANES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANALEPTICS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM AGENTS
DRUGS
ENZYMES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LYASES
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NEUROREGULATORS
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
REACTION KINETICS
RODENTS
SYMPATHOMIMETICS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques