Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-9-18
pubmed:abstractText
The 5-hydroxytryptamine (5-HT)2A receptor is an important component of the neural substrates underlying ethanol (EtOH) intake and behaviors related to anxiety and stress. Paradoxically, both 5-HT2A agonists and antagonists have been shown to reduce EtOH intake, however the mechanisms underlying these effects are not understood. This inconsistency could possibly be explained by their chronic down-regulation of the 5-HT2A receptor. To further address these findings, the present study sought to functionally characterize the role of localized 5-HT2A receptors in regulating EtOH ingestion by producing central nervous system site-specific receptor down-regulation through infusion of antisense oligonucleotide (ASO). Rats were infused with 5-HT2A receptor ASO into the lateral ventricle (i.c.v.), prefrontal cortex (PFC), central amygdaloid nucleus, medial and lateral division (CeA/L), dorsal raphe nucleus (DRN), or hippocampus (HIP) for a period of 26 days. Subjects were tested for EtOH intake and behaviors related to anxiety and stress. ASO administration i.c.v. and into the CeA/L significantly reduced EtOH intake. PFC 5-HT2A ASO administration increased EtOH intake. Administration of 5-HT2A ASO into the DRN and HIP had no effect on EtOH intake. Intracerebroventricular ASO administration increased activity in a novel open field and increased anxiety-like behavior in the elevated plus maze. PFC ASO administration produced an anxiogenic effect in the elevated plus maze. Intracerbroventricular, PFC, and CeA/L ASO infusions altered adrenocortical function. These differential behavioral effects specific to the anatomical locations targeted for 5-HT2A receptor down-regulation may help resolve a long-standing, apparent inconsistency in the role of 5-HT2A receptors in EtOH consumption.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
277-89
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11561090-Alcohol Drinking, pubmed-meshheading:11561090-Amphetamines, pubmed-meshheading:11561090-Animals, pubmed-meshheading:11561090-Anxiety, pubmed-meshheading:11561090-Autoradiography, pubmed-meshheading:11561090-Brain Chemistry, pubmed-meshheading:11561090-Corticosterone, pubmed-meshheading:11561090-Down-Regulation, pubmed-meshheading:11561090-Male, pubmed-meshheading:11561090-Motor Activity, pubmed-meshheading:11561090-Mutation, Missense, pubmed-meshheading:11561090-Oligonucleotides, Antisense, pubmed-meshheading:11561090-Pain Measurement, pubmed-meshheading:11561090-Rats, pubmed-meshheading:11561090-Rats, Long-Evans, pubmed-meshheading:11561090-Receptor, Serotonin, 5-HT2A, pubmed-meshheading:11561090-Receptors, Serotonin, pubmed-meshheading:11561090-Saccharin, pubmed-meshheading:11561090-Serotonin Antagonists, pubmed-meshheading:11561090-Stress, Psychological, pubmed-meshheading:11561090-Taste, pubmed-meshheading:11561090-Time Factors
pubmed:year
2001
pubmed:articleTitle
Bidirectional changes in ethanol consumption in rats with site-specific antisense down-regulation of 5-hydroxytryptamine2A receptors in brain.
pubmed:affiliation
Division of Neuropharmacology, Center of Alcohol Studies, Rutgers University, Piscataway, New Jersey 08854-8100, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.