PMID- 12654345
OWN - NLM
STAT- MEDLINE
DCOM- 20030610
LR  - 20190712
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 117
IP  - 4
DP  - 2003
TI  - 5-hydroxytryptamine(2A) receptors regulate sympathetic nerves constricting the 
      cutaneous vascular bed in rabbits and rats.
PG  - 939-48
AB  - Hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) is partially due 
      to sympathetically-mediated cutaneous vasoconstriction that impairs normal heat 
      dissipation. MDMA acts by releasing monoamines, including 5-hydroxytryptamine 
      (5-HT), but receptor mechanisms underlying MDMA-elicited hyperthermia and 
      cutaneous vasoconstriction are not known. The specific 5-HT2A agonist 
      (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is a potent 
      hallucinogen that also causes marked hyperthermia, suggesting the possibility 
      that DOI, via stimulation of 5-HT2A receptors, might also cause sympathetically 
      mediated cutaneous vasoconstriction. We tested this hypothesis in conscious 
      unrestrained rabbits and rats. Blood flow was assessed by chronically implanted 
      Doppler ultrasonic flow probes. Body temperature was measured by i.p. telemetric 
      probes. We compared effects of DOI on cutaneous blood flow (ear pinna in rabbits, 
      tail in rats) with effects on mesenteric blood flow and arterial 
      pressure.Hyperthermia induced by DOI (5-100 microgram/kg i.v. in rabbits and 100 
      microgram/kg s.c. in rats) was preceded and accompanied by markedly reduced blood 
      flow to the cutaneous bed, with no change in flow to the mesenteric bed. In 
      rabbits, DOI (5 microgram/kg i.v.) did not affect arterial pressure or heart 
      rate. DOI (100 microgram/kg i.v.) caused a moderate rise in arterial pressure. In 
      rabbits, the 5-HT2A receptor antagonists ketanserin (0.3 mg/kg i.v.) and AC90179 
      (0.5 mg/kg i.v.) reversed the ear pinna vasoconstriction induced by DOI (5 
      microgram/kg i.v.). In rats, ketanserin (3 mg/kg s.c.) reversed tail 
      vasoconstriction and hyperthermia induced by DOI (100 microgram/kg s.c.). In 
      rabbits, the cutaneous vasoconstricting effect of DOI (5 microgram/kg i.v.) was 
      substantially abolished in the ipsilateral ear pinna after interruption of 
      preganglionic sympathetic nerve activity by unilateral section of the cervical 
      sympathetic trunk. Thus hyperthermia evoked by direct stimulation of 5-HT2A 
      receptors is associated with marked sympathetically mediated vasoconstriction, 
      selective for the cutaneous bed. Impairment of the ability to dissipate heat 
      following drug-induced stimulation of 5-HT2A receptors is likely to contribute to 
      hyperthermia induced by MDMA and by hallucinogenic drugs such as LSD.
FAU - Blessing, W W
AU  - Blessing WW
AD  - Department of Physiology, Centre for Neuroscience, Flinders Medical Centre, 
      Flinders University, 5042 SA, Bedford Park, Australia. 
      w.w.blessing@flinders.edu.au
FAU - Seaman, B
AU  - Seaman B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Hallucinogens)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (dimethoxy-4-indophenyl-2-aminopropane)
RN  - 333DO1RDJY (Serotonin)
RN  - 500-85-6 (Indophenol)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects/physiology
MH  - Blood Vessels/drug effects/*innervation/physiology
MH  - Body Temperature/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Fever/chemically induced/*metabolism/physiopathology
MH  - Hallucinogens/adverse effects
MH  - Indophenol/*analogs & derivatives/pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/adverse effects
MH  - Rabbits
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Serotonin, 5-HT2A
MH  - Receptors, Serotonin/drug effects/*metabolism
MH  - Regional Blood Flow/drug effects/physiology
MH  - Serotonin/metabolism
MH  - Serotonin Antagonists/pharmacology
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Skin/*blood supply
MH  - Sympathectomy
MH  - Sympathetic Fibers, Postganglionic/drug effects/*metabolism
MH  - Vasoconstriction/drug effects/*physiology
EDAT- 2003/03/26 05:00
MHDA- 2003/06/11 05:00
CRDT- 2003/03/26 05:00
PHST- 2003/03/26 05:00 [pubmed]
PHST- 2003/06/11 05:00 [medline]
PHST- 2003/03/26 05:00 [entrez]
AID - S0306452202008102 [pii]
AID - 10.1016/s0306-4522(02)00810-2 [doi]
PST - ppublish
SO  - Neuroscience. 2003;117(4):939-48. doi: 10.1016/s0306-4522(02)00810-2.