Central versus peripheral effects on temperature preference and body temperature following alteration of 5-HT in maturing mice.
Experiments were designed to distinguish between central and peripheral effects on temperature preference and body temperature of drugs injected intraperitoneally (IP) in infant mice ranging in age from 3 to 10 days postpartum. These compared a drug restricted to the periphery ("peripheral" drug) with a drug of similar action that reaches the central nervous system (CNS) as well as the periphery. Two different classes of drugs were utilized to test central versus peripheral actions independently with drugs that have different modes of action: 1-aromatic amino acid inhibitors and serotonin receptor antagonists. Although the decarboxylase inhibitor NSD 1015, which reaches the central nervous system from IP injection, can significantly decrease temperature preference (Tpref), the peripheral inhibitor carbidopa had no significant effects on Tpref or on body temperature (Tb). Furthermore, pretreatment with NSD 1015 prevented the elevation of Tpref produced by the serotonin precursor 5-hydroxytryptophan (5-HTP); however carbidopa pretreatment had no effect on the increased Tpref produced by 5-HTP. In other experiments, the peripheral serotonin antagonist BW 501C was not able to prevent elevated Tpref produced by 5-HTP, although the specific 5-HT2 antagonist pirenperone, which reaches the CNS as well as the periphery, blocks the 5-HTP elevation of Tpref. Taking all of these results together, we conclude that the changes in Tb and Tpref following these treatments require a decarboxylase inhibitor or 5-HT antagonist that reaches the CNS. However, the well known and potent peripheral vasoconstrictor action of serotonin requires that peripheral effects of drugs be considered when manipulations are not restricted to the CNS.
Goodrich
C
C
Department of Biology, Cleveland State University, OH 44115.
Lechner
R
R
Slone
W
W
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects*; D002230:Carbidopa / Q000494:pharmacology; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D004347:Drug Interactions; D006834:Hydrazines / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D051379:Mice; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000578:Amidines; D006834:Hydrazines; D010880:Piperidines; D012702:Serotonin Antagonists; C029751:BW 501C; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D002262:Carboxy-Lyases; D002230:Carbidopa; C034177:pirenperone