Effects of chronic cocaine administration on [3H]dopamine uptake in the nucleus accumbens, striatum and frontal cortex of rats. 1994

J M Masserano, and D Venable, and R J Wyatt
Neuropsychiatry Branch, National Institute of Mental Health Neurosciences Center at St. Elizabeths, Washington, District of Columbia.

The uptake of [3H]dopamine into synaptosomes obtained from the nucleus accumbens, striatum and frontal cortex was evaluated after chronic treatment with cocaine. Cocaine was administered in a concentration of 10 mg/kg, twice a day for 7 days. Fourteen days after the last injection, locomotor activity and [3H] dopamine uptake were evaluated. Base-line locomotor activity was significantly lower (29%) in rats treated chronically with cocaine compared with saline-treated rats. A challenge dose of cocaine (2.5 mg/kg or 5.0 mg/kg) or d-amphetamine (1 mg/kg) produced similar increases in locomotor activity above the corresponding base-line values in both saline- and cocaine-treated rats, indicating that behavioral sensitization had not occurred. Chronic cocaine administration produced a significant decrease in the uptake of [3H]dopamine into the frontal cortex (49%) with no significant differences in the nucleus accumbens or striatum. The decrease in [3H]dopamine uptake in the frontal cortex was due to a decrease in the Vmax with no change in the affinity of [3H]dopamine for the dopamine transporter. No differences were produced in the IC50 values of GBR 12909 or cocaine for [3H] dopamine uptake after chronic cocaine treatment. However, in all three brain regions, the IC50 values for cocaine were significantly greater than the values for GBR 12909. In addition, the IC50 values for GBR 12909 and cocaine in the frontal cortex were significantly greater than values for either compound in the nucleus accumbens or striatum. The administration of methamphetamine, using a similar treatment schedule, produced no changes in [3H]dopamine uptake in any of the three brain areas. These data indicate an inhibition effect of repeated cocaine administration on [3H]dopamine uptake in the frontal cortex of rats.

UI MeSH Term Description Entries
D008297 Male Males
D008694 Methamphetamine A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. Deoxyephedrine,Desoxyephedrine,Desoxyn,Madrine,Metamfetamine,Methamphetamine Hydrochloride,Methylamphetamine,N-Methylamphetamine,Hydrochloride, Methamphetamine,N Methylamphetamine
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009714 Nucleus Accumbens Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA. Accumbens Nucleus,Nucleus Accumbens Septi,Accumbens Septi, Nucleus,Accumbens Septus, Nucleus,Accumbens, Nucleus,Nucleus Accumbens Septus,Nucleus, Accumbens,Septi, Nucleus Accumbens,Septus, Nucleus Accumbens
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical

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