The role of 5-hydroxytryptamine1A (5-HT1A) receptors in the anticonflict activity of beta-adrenoceptor antagonists.
Using the conflict drinking test as a model, we studied in rats the effect of the nonselective beta-adrenoceptor blockers pindolol and cyanopindolol which bind to 5-HT1A and 5-HT1B receptors, and of the selective beta 1- and beta 2-adrenoceptor antagonists betaxolol and ICI 118,551, respectively, which have a negligible affinity for 5-HT receptors. Both pindolol (2.0-8.0 mg/kg) and cyanopindolol (0.5-2.0 mg/kg) showed an anticonflict effect, having dose dependently increased the number of punished licks. On the other hand, neither betaxolol nor ICI 118,551--administered separately or in combination--affected the punished responding. The anticonflict effects of pindolol and cyanopindolol were completely abolished by the 5-HT1A receptor and alpha 1-adrenoceptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phtalimmido)butyl]piperazine (NAN-190), but were not modified by the selective alpha 1(-)-adrenoceptor antagonist prazosin. The effects of pindolol and cyanopindolol were also not modified in animals with lesions of 5-HT neurons, produced by p-chloroamphetamine (PCA). Moreover, it was also found that the anticonflict effects of pindolol and cyanopindolol in PCA-pretreated rats were antagonized by NAN-190 but not prazosin. Our results indicate that the anticonflict effects of pindolol and cyanopindolol depend on their agonist action on postsynaptic 5-HT1A receptors.
Przegaliński
E
E
Polish Academy of Sciences, Institute of Pharmacology, Kraków.
Filip
M
M
Chojnacka-Wójcik
E
E
Tatarczyńska
E
E
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D015784:Betaxolol / Q000494:pharmacology; D003220:Conflict, Psychological; D004195:Disease Models, Animal; D004347:Drug Interactions; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D010879:Piperazines; D011412:Propanolamines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C026777:ICI 118551; C047975:cyanopindolol; D010133:p-Chloroamphetamine; D010869:Pindolol; D015784:Betaxolol; D011224:Prazosin