Beta-adrenoceptor blockade in rats enhances the ambulation induced by 5-HT1A receptor agonists.
The mixed beta-adrenoceptor and 5-HT1A receptor antagonists, (-)-pindolol and propranolol, enhance rather than inhibit the hyperlocomotion induced in rats by the 5-HT1A receptor agonist, 8-OH-DPAT. The mechanism of this effect was now investigated. The rats were pretreated with the beta-adrenoceptor antagonist or saline and with the agonist 45 min later. Ambulation was quantified as the number of quadrants entered during a 15 min observation period. (-)-Pindolol, alprenolol, betaxolol, ICI 118,551 and a combination of betaxolol and ICI 118,551 (all at 1 mg/kg) significantly enhanced the locomotion induced by 8-OH-DPAT (0.24 mg/kg). Timolol (1 and 10 mg/kg) given 45 min before 8-OH-DPAT was inactive; however, given at 10 mg/kg 15 min prior to 8-OH-DPAT, the compound enhanced locomotion. (-)-Pindolol (1 mg/kg) also enhanced the locomotion induced by the putative selective 5-HT1A receptor partial agonists, flesinoxan and ipsapirone, but not that induced by 5-OH-DPAT, a DA2 receptor agonist. These results suggest that beta 1- or beta 2-adrenoceptor antagonism can enhance the locomotion induced by 5-HT1A receptor agonists. In the case of mixed 5-HT1A and beta-adrenoceptor antagonists, the beta-adrenoceptor-mediated effect may mask the inhibition of locomotion expected from 5-HT1A receptor antagonism.
Kalkman
H O
HO
Preclinical Research Sandoz AG, Basel, Switzerland.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C056895:flesinoxan; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol