Biomaterial Database

Active versus passive cocaine administration: differences in the neuroadaptive changes in the brain dopaminergic system. 2007

Roman Stefański, and Barbara Ziółkowska, and Maciej Kuśmider, and Paweł Mierzejewski, and Edyta Wyszogrodzka, and Paulina Kołomańska, and Marta Dziedzicka-Wasylewska, and Ryszard Przewłocki, and Wojciech Kostowski

Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warsaw, Poland.

There is considerable evidence that chronic exposure to cocaine is associated with low striatal dopamine D2 receptor availability. In the present study we wished to determine whether neuroadaptive changes in densities of D2 receptors were due to direct pharmacological actions of cocaine or they reflected motivational states that were present when cocaine injection depended on active drug-seeking behavior and whether these changes were related to the actual expression of D2 mRNA. To achieve this goal we utilized a "yoked" procedure in which rats were tested simultaneously in groups of three, with only one rat actively self-administering cocaine while the other two received yoked injections of either cocaine or saline. Only passively administered cocaine produced a decrease in dopamine D2 receptor levels in the anterior and central regions of caudate/putamen, and both the shell and core of the nucleus accumbens, as measured by in vitro quantitative autoradiography. In contrast, examination of D2 receptor gene expression using in situ hybridization analysis revealed that there was an increase in D2 receptor mRNA levels in the ventral tegmental area of rats actively self-administered cocaine. We conclude that the reductions in striatal D2 receptor densities may be related to the chronic administration of cocaine per se and not to the motivated process of reinforced responding. Our results also suggest that increases in D2 receptor mRNA levels in limbic regions do not necessarily result in increased receptor densities and these changes likely reflect motivational states that were present when cocaine injection dependent on active drug self-administration.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009434	Neural Pathways	Neural tracts connecting one part of the nervous system with another.	Neural Interconnections,Interconnection, Neural,Interconnections, Neural,Neural Interconnection,Neural Pathway,Pathway, Neural,Pathways, Neural
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
D012054	Reinforcement, Psychology	The strengthening of a conditioned response.	Negative Reinforcement,Positive Reinforcement,Psychological Reinforcement,Reinforcement (Psychology),Negative Reinforcements,Positive Reinforcements,Psychological Reinforcements,Psychology Reinforcement,Psychology Reinforcements,Reinforcement, Negative,Reinforcement, Positive,Reinforcement, Psychological,Reinforcements (Psychology),Reinforcements, Negative,Reinforcements, Positive,Reinforcements, Psychological,Reinforcements, Psychology
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
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
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000222	Adaptation, Physiological	The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT.	Adaptation, Physiologic,Adaptations, Physiologic,Adaptations, Physiological,Adaptive Plasticity,Phenotypic Plasticity,Physiological Adaptation,Physiologic Adaptation,Physiologic Adaptations,Physiological Adaptations,Plasticity, Adaptive,Plasticity, Phenotypic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia