Effects of cocaine on norepinephrine stimulated phosphoinositide hydrolysis and locomotor activity in rat

Miscellaneous · Sun Jan 01 00:00:00 EST 1989

OSTI ID:5476330

Mosaddeghi, M

The function of {alpha}{sub 1}-adrenoceptors was determined by stimulating cortical tissue slices, which were pre-labeled with ({sup 3}H)inositol, with norepinephrine (NE) in the presence of 8 mM LiCl. Results of in vitro studies showed that cocaine 10 {mu}M potentiated maximal NE-stimulated PI hydrolysis by 30%. In addition, the EC{sub 50} was decreased from 3.93 {plus minus} 0.42 to 1.91 {plus minus} 0.31 {mu}M NE. Concentrations of 0.1-100 {mu}M and 0.1-10 {mu}M cocaine enhanced PI hydrolysis stimulated by 0.3 and 3 {mu}M NE, respectively. The concentration-effect curves for NE-stimulated PI hydrolysis were shifted to the right 100-fold in the presence of 0.1 {mu}M prazosin. Cocaine (10 {mu}M) did not potentiate NE-stimulated PI hydrolysis in the presence of 0.1 {mu}M prazosin. ({sup 3}H)Prazosin saturation and NE ({sup 3}H)prazosin competition binding studies using crude membrane preparations showed that 10 {mu}M cocaine did not alter binding parameters B{sub max}, K{sub d}, Hill slope, and IC{sub 50}. Together, these results implied that cocaine in vitro potentiated NE-stimulated PI hydrolysis by blocking NE reuptake. For in vivo studies, the locomotor activity was determined after an acute or chronic injections of either cocaine or saline. Cocaine or saline-treated rats were killed after measurement of the locomotor activity, and NE-stimulated PI hydrolysis was measured. Acute administration of cocaine 3.2-42 mg/kg (i.p.) produced an inverted U shaped dose-response curve on locomotor activity. The peak increase in locomotor activity was at 32 mg/kg cocaine. A dose of 42 mg/kg cocaine produced a significant depression of maximal NE-stimulated PI hydrolysis.

• Research Organization: Louisiana State Univ., New Orleans, LA (United States). Medical Center
• OSTI ID: 5476330
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
COCAINE
BIOLOGICAL EFFECTS
PHOSPHOLIPIDS
METABOLISM
SYMPATHOMIMETICS
RECEPTORS
BEHAVIOR
BIOCHEMICAL REACTION KINETICS
INOSITOL
NORADRENALINE
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ALKALOIDS
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBOHYDRATES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ESTERS
HORMONES
HYDROGEN COMPOUNDS
INOSITOLS
ISOTOPE APPLICATIONS
KINETICS
LIPIDS
MAMMALS
MEMBRANE PROTEINS
MONOSACCHARIDES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PROTEINS
PSYCHOTROPIC DRUGS
REACTION KINETICS
RODENTS
SACCHARIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques