Nicotine induced c-fos expression in the striatum is mediated mostly by dopamine D1 receptor and is dependent on NMDA stimulation. 1994

H Kiba, and A Jayaraman
Department of Neurology, LSU School of Medicine, New Orleans 70112.

The powerful psychostimulant and positive reinforcing effects of nicotine have been speculated to be mediated by the dopaminergic neurons of the ventral tegemental area (VTA) and their terminals in the nucleus accumbens. To extend our understanding of nicotine and dopamine interactions, we mapped the pattern of c-fos expression in the striatum as an important marker of some of the earliest changes that occur at gene transcription level. Acute nicotine injections in rats led to Fos expression more prominently in the caudatoputamen than in the nucleus accumbens in a dose-dependent fashion. Fos-reactive cells were more prominent in the central and dorsomedial limbic caudatoputamen than in the dorsolateral sensory-motor striatum. Injections of mecamylamine completely blocked nicotine-induced Fos expression. Injections of the selective dopamine D1 antagonist SCH 23390, but not D2 antagonist YM 09151-2 or Clozapine, a drug with high affinity to D4 receptors, before nicotine injections, completely blocked Fos expression in the striatum. Nicotine induced Fos expression was also blocked completely by the NMDA receptor antagonists MK-801 and CPP. These results suggest that nicotine-induced Fos expression in the striatum is mediated mostly by dopamine D1 receptors and that the Fos expression is also dependent on N-methyl-D-aspartate (NMDA) stimulation.

UI MeSH Term Description Entries
D008297 Male Males
D008464 Mecamylamine A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.
D009538 Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Nicotine Bitartrate,Nicotine Tartrate
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.
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D003024 Clozapine A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Clozaril,Leponex
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
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
D005971 Glutamates Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Glutamic Acid Derivatives,Glutamic Acids,Glutaminic Acids

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