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Blockade of stimulant-induced preprodynorphin mRNA expression in the striatal matrix by serotonin depletion. 2005

K A Horner, and D H Adams, and G R Hanson, and K A Keefe
Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, UT 84112, USA. kristen.horner@pharm.utah.edu

Cocaine and methamphetamine (METH) induce preprodynorphin (PPD) mRNA expression in the striatum. Cocaine induces PPD expression in both the patch and matrix compartments of the rostral striatum, whereas METH induces PPD expression in the patch compartment of the rostral striatum. In middle striatum, both stimulants increase PPD expression in the patch and matrix compartments. METH and cocaine treatment also increase extracellular serotonin (5-HT). Several studies have shown that 5-HT receptors are present on striatonigral neurons that express PPD mRNA, and that 5-HT is a positive regulator of striatal neuropeptide expression. The current study examined whether 5-HT plays a role in the patch/matrix expression of PPD mRNA induced by cocaine and METH in striatum. Male Sprague-Dawley rats were treated with p-chloroamphetamine (PCA; 8 mg/kg, i.p), a serotonin neurotoxin, 1 week prior to cocaine (30 mg/kg, i.p) and METH (15 mg/kg, s.c.) treatment. The 80% loss of 5-HT induced by PCA-pretreatment blocked cocaine-induced PPD expression in the rostral matrix compartment. Cocaine- and METH-induced PPD expression in the rostral patch compartment was unaffected by PCA-pretreatment. PCA-pretreatment also decreased both cocaine- and METH-induced PPD expression in the matrix, but not patch of middle striatum. PCA-induced 5-HT depletion did not affect stimulant-induced increases in PPT mRNA expression in the striatum. These data suggest that 5-HT plays a role in stimulant-induced PPD expression in the matrix compartment of rostral and middle striatum. Thus, 5-HT innervation may play a critical role in basal ganglia function.

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
D010133 p-Chloroamphetamine Chlorinated analog of AMPHETAMINE. Potent neurotoxin that causes release and eventually depletion of serotonin in the CNS. It is used as a research tool. p-Chloramphetamine,para-Chloroamphetamine,LY-121860,Ly-123362,Parachloroamphetamine,LY 121860,LY121860,Ly 123362,Ly123362,p Chloramphetamine,p Chloroamphetamine,para Chloroamphetamine
D011498 Protein Precursors Precursors, Protein
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
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
D004399 Dynorphins A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters. Dynorphin,Dynorphin (1-17),Dynorphin A,Dynorphin A (1-17)
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
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

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