Genomic responses to 5-HT1A or 5-HT2A/2C receptor activation is differentially regulated in four regions of rat brain.
The functional profiles of brain 5-HT1A and 5-HT2A/C receptors were assessed by quantitating changes in the immediate early genes -c-fos, ngf1c and tis1, following receptor activation with either 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane). Stimulation of either class of 5-HT receptor elicited an induction of all three immediate early genes to varying extents in cortex, hippocampus and cerebellum, but not in striatum. The responses to 8-OH-DPAT peaked earlier than those to DOI. WAY 100135 (N-tertiobutyl-3-[4-(2-methoxyphenyl)-piperazinyl]-2-phenylpropana mide), the putative 5-HT1A receptor antagonist blocked the 8-OH-DPAT effect but not the responses to DOI. WAY 100135 by itself also elicited a relatively smaller genomic response. Ketanserin completely abolished the DOI-induced genomic responses. The results support the earlier findings that 5-HT1A receptor sites are abundant in frontal cortex and hippocampus. In addition, the robust genomic responses to 8-OH-DPAT as well as Northern hybridization with a cDNA probe for 5-HT1A mRNA in the cerebellum clearly implicate the functional expression of 5-HT1A receptors in this brain region. The responses to the 5-HT2 receptor agonist, DOI support a greater abundance of these receptors in the cortex, and relatively lower levels in hippocampus and cerebellum. The results suggest a differential induction pattern among the three immediate-early genes depending on the brain region and the 5-HT receptor subtype involved.
Tilakaratne
N
N
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Friedman
E
E
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early / Q000502:physiology*; D016762:Genes, fos / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000235:genetics* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000662:Amphetamines; D015342:DNA Probes; D010879:Piperazines; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C081293:WAY 100135; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine