The effects of beta-antagonists and anxiolytics on conflict behavior in the rat.
The present studies were designed to evaluate the effects of beta-adrenoceptor antagonists and traditional anxiolytics (phenobarbital and diazepam), alone and in combination, on behavior in the Conditioned Suppressioned of Drinking (CSD) conflict paradigm, an "animal model" for the study of anxiety and antianxiety agents. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.5 mA), electrification being signalled by the presence of a tone. Within 2-3 weeks, control responding had stabilized (10-15 shocks/session and 10-15 ml water/session); drug tests were then conducted at weekly intervals. As expected, diazepam (0.6-10 mg/kg) and phenobarbital (10-40 mg/kg) administration resulted in a marked and dose-dependent increase in punished responding at doses which did not markedly alter background responding (water intake). Neither propranolol (0.5-8 mg/kg) nor the beta-1-selective antagonist atenolol (1-16 mg/kg) significantly affected punished responding in the CSD. Both propranolol and atenolol produced significant beta-1-adrenoceptor blockade, as evidenced by the production of significant bradycardic effects in conscious rats at the doses employed. Pretreatment with 2.0 mg/kg propranolol did not alter the anticonflict effects of diazepam (0.6-10 mg/kg) or phenobarbital (10-40 mg/kg). Further, reduction of the shock intensity to 0.125 mA (i.e., decreased suppression) failed to alter the behavioral response to propranolol (1.5-5 mg/kg) or the interaction of 2.0 mg/kg propranolol with diazepam. Finally, chronic administration of propranolol (2.0 mg/kg, twice daily) did not affect punished responding over the course of 5 weeks of treatment. These data suggest that the CSD paradigm, although an effective "animal model" for the study of benzodiazepine and barbiturate anticonflict effects, cannot serve as an "animal model" for the study of the situation-specific (i.e., phobic) anxiety for which propranolol and related agents are presently used.
Fontana
D J
DJ
Department of Pharmaceutical Sciences, College of Pharmacy & AHP, Wayne State University, Detroit, MI 48202.
McCloskey
T C
TC
Jolly
S K
SK
Commissaris
R L
RL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects; D005260:Female; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D014151:Anti-Anxiety Agents; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D003975:Diazepam