The 5-HT1A receptor modulates the effects of cocaine on extracellular serotonin and dopamine levels in the nucleus accumbens. 2005

Christine M Andrews, and Hank F Kung, and Irwin Lucki
Institute of Neurological Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.

The regulation of extracellular levels of serotonin (5-HT) and dopamine in response to cocaine by 5-HT1A receptors was examined using in vivo microdialysis and the 5-HT1A receptor antagonist 4-(2'-methoxy-)-phenyl-1-[2'-(N-2''-pyridinyl)-p-fluorobenzamido-]ethyl-piperazine (p-MPPF). Pretreatment with p-MPPF significantly augmented the increase in extracellular levels of both 5-HT and dopamine in the nucleus accumbens produced by systemic administration of cocaine. Levels of 5-HT or dopamine were unaffected by p-MPPF given alone. Extracellular levels of 5-HT and dopamine were increased dramatically by cocaine infused locally into the nucleus accumbens. Systemic injection of cocaine given during the cocaine infusion reduced 5-HT and dopamine levels, presumably by activating inhibitory 5-HT and dopamine autoreceptors outside of the locus of infusion. The reduction of 5-HT and dopamine levels by systemic cocaine during accumbal infusion was blocked by pretreatment with the 5-HT1A receptor antagonist p-MPPF. Taken together, these findings suggest that the 5-HT1A autoreceptor acts to modulate the effects of cocaine on both 5-HT and dopamine levels in the nucleus accumbens.

UI MeSH Term Description Entries
D008297 Male Males
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.
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
D005110 Extracellular Space Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall. Intercellular Space,Extracellular Spaces,Intercellular Spaces,Space, Extracellular,Space, Intercellular,Spaces, Extracellular,Spaces, Intercellular
D000631 Aminopyridines Pyridines substituted in any position with an amino group. May be hydrogenated but must retain at least one double bond. Aminopyridine
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
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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