Activation of 5-HT1A and 5-HT7 receptors in the parafascicular nucleus suppresses the affective reaction of rats to noxious stimulation.
The antinociceptive effects of the serotonin (5-HT)1A/7 receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) administered into the medial thalamus were evaluated. Pain behaviors organized at spinal (spinal motor reflexes, SMRs), medullary (vocalizations during shock, VDSs), and forebrain (vocalization after discharges, VADs) levels of the neuraxis were elicited by tailshock. Administration of 8-OH-DPAT (5, 10, and 20 microg/side) into nucleus parafascicularis (nPf) produced dose-dependent increases in VDS and VAD thresholds, but failed to elevate SMR threshold. The increase in VAD threshold was significantly greater than that of VDS threshold. Similar effects were observed with administration of 8-OH-DPAT (20 microg/side) into the rostral portion of the central lateral thalamic nucleus. The bilateral or unilateral administration of 8-OH-DPAT (20 microg) into other thalamic nuclei, or into sites dorsal to nPf, did not elevate vocalization thresholds. Increases in vocalization thresholds produced by nPf-administered 8-OH-DPAT were mediated by both 5-HT1A and 5-HT7 receptors. Intra-nPf administration of the 5-HT1A receptor antagonist WAY-100635 (0.05 or 0.5 microg/side), or the 5-HT7 receptor antagonist SB-269970 (1 or 2 microg/side), but not the dopamine D2 receptor antagonist raclopride (10 microg/side), reversed 8-OH-DPAT induced elevations in vocalization thresholds. These results provide the first reported evidence of behavioral antinociception following the administration of a 5-HT agonist into the medial thalamus.
Harte
Steven E
SE
Department of Psychology, Behavioral and Cognitive Neuroscience Program, Wayne State University, 71 W. Warren Ave., Detroit, MI 48202, USA.
Kender
Robert G
RG
Borszcz
George S
GS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000339:Affect / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007839:Functional Laterality; D020646:Intralaminar Thalamic Nuclei / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D010812:Physical Stimulation / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014828:Vocalization, Animal / Q000187:drug effects
D018492:Dopamine Antagonists; D010636:Phenols; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D020891:Raclopride; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin