The relation of central 5-HT1A and 5-HT2 receptors: low dose agonist-induced selective tolerance in the rat.
To study the purported relation of 5-HT1A and 5-HT2 receptors, we chronically injected rats with a low dose of selective 5-HT agonists to induce behavioral tolerance and then tested for cross-tolerance. Acutely, in naive rats, both the putative 5-HT2 agonist DOI and 5-HT1A agonist 8-OH-DPAT induced some behaviors of the "serotonin syndrome" but the two drugs could be differentiated. Only DOI evoked shaking behavior, "skin jerks" (spinal myoclonus), and hyperthermia. Only 8-OH-DPAT induced flat body posture, head weaving, hypothermia, and occasional hindlimb hyperextension (dystonic posture). Both drugs, especially 8-OH-DPAT, evoked forepaw tapping. Chronic (21 day) treatment with DOI prevented DOI-evoked behaviors but not behaviors evoked by 8-OH-DPAT. Behaviors evoked by 8-OH-DPAT and not DOI decreased significantly after chronic 8-OH-DPAT treatment. Development of selective tolerance suggests that putative selective 5-HT2 and 5-HT1A agonists exert both shared and distinctive behavioral effects through separate sites whose relation is behavior-specific. For some behaviors (forepaw myoclonus, shaking behavior, thermoregulation), there is a functional interaction between 5-HT1A and 5-HT2 sites, while for other behaviors (skin jerks, flat body posture, head weaving), there is no interaction.
Pranzatelli
M R
MR
Department of Neurology, George Washington University, Washington, DC 20010.
Pluchino
R S
RS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D004361:Drug Tolerance; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009207:Myoclonus / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine