Behavioral consequences of activation of beta adrenergic receptors by clenbuterol: evidence for mediation by the central nervous system.
The centrally acting beta adrenergic agonist clenbuterol has been shown to produce specific effects on behavior maintained under differential-reinforcement-of-low-rate and multiple fixed-interval/fixed-ratio schedules. In the present study, experiments were carried out to determine whether these effects of clenbuterol were mediated by beta adrenergic receptors in the brain or in the periphery. This was accomplished by comparing the antagonistic potencies of the beta adrenergic antagonists propranolol and CGP-12177, following systemic administration. These compounds were found to exhibit similar affinities for beta adrenergic receptors in vitro. They also inhibited 125I-pindolol binding, in vivo, to rat heart and lung with similar potencies. By contrast, CGP-12177, being hydrophilic relative to propranolol, was approximately 100-fold less potent than propranolol at inhibiting 125I-pindolol binding in cerebral cortex and cerebellum, in vivo. The potencies of propranolol and CGP-12177 for antagonizing the behavioral effects of clenbuterol also were determined. CGP-12177 was about 40-fold less potent than propranolol at antagonizing the behavioral effects of clenbuterol. These results suggest that the changes in the goal-oriented behaviors produced by clenbuterol were predominantly a result of activation of central, rather than peripheral, beta adrenergic receptors. For this reason, it appears that centrally acting beta adrenergic agonists like clenbuterol may be useful pharmacological tools to study the relationship between activation of central beta adrenergic receptors and behavior.
O'Donnell
J M
JM
Life Sciences Division, Los Alamos National Laboratory, NM 87545.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002976:Clenbuterol / Q000378:metabolism / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D008297:Male; D010869:Pindolol / Q000378:metabolism / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D010869:Pindolol; C033394:CGP 12177; D002976:Clenbuterol