Psychotropic effects of adrenergic beta-blockers on agonistic behavior between resident and intruder mice.
ABSTRACT The present study was conducted to investigate the effect of adrenergic beta-blockers on agonistic behavior in male mice, using quantitative ethological methods. Agonistic behavior was evoked using a resident-intruder paradigm. The following drugs were administered orally at four dose levels (vehicle, 5, 10 and 20 mg/kg) to either resident or intruder mice: dl-propranolol, practolol, d-propranolol, and l-propranolol. When the resident was treated with either dl-propranolol or l-propranolol, aggressive episodes (offensive sideways posture, attack bite, tail rattle) were suppressed significantly in a dose-dependent manner, whereas practolol and d-propranolol were ineffective. All treatments except the high dose of l-propranolol failed to affect the resident's solitary behavior (locomotion). When the intruder was treated with beta-blockers, agonistic behavior was not altered. Since practolol does not cross the blood-brain barrier, the differential suppression of agonistic behavior is due to the central action of beta-blockers. d-Propranolol does cross the blood-brain barrier but is devoid of beta-receptor blocking property; hence l-propranolol suppression of agonistic behavior implies inactivation of brain adrenergic beta-receptors. The findings seem to indicate that beta-blockers such as dl-propranolol and l-propranolol have a psychotropic action.
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ABSTRACT: The relative importance of 5-HT1A and β-adrenergic activities in the antiaggressive effects of (−)-penbutolol was studied in male mice. (−)-Penbutolol had high affinity for 5-HT1A receptors and β-adrenoceptors, and antagonized the 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced 5-HT syndrome and the 8-hydroxy-2-(di-n-propylamin)tetralin (8-OH-DPAT)-induced discriminatory stimulus in rats. (−)-Penbutolol abolished aggressive behaviour (ED50 = 56 μmol/kg), and reversed the antiaggressive effects of 8-OH-DPAT and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) (ED50 = 8.1 and 2.1 μmol/kg, respectively). (N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635) reversed the antiaggressive effects of 8-OH-DPAT (ED50 = 0.012 μmol/kg), but did not affect the antiaggressive effects of TFMPP. The antiaggressive effect of a submaximal dose of 8-OH-DPAT was markedly potentiated by β-adrenoceptor antagonists without 5-HT1A receptor affinity, whereas (−)-penbutolol was effective at only one dose (4.5 μmol/kg). In conclusion, the 5-HT1A receptor antagonistic potency of (−)-penbutolol in aggressive mice is attenuated by β-adrenoceptor-induced facilitation of serotonergic neurotransmission.European Journal of Pharmacology 03/1996; · 2.59 Impact Factor
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ABSTRACT: The effects of dl-propranolol on the behaviour of adult male CD1 mice were examined after acute intraperitoneal injection (1.5 and 6 mg/kg) and after administration for 10-13 days in the drinking fluid at 12.4 mg/l (1.9 mg/kg daily) and 24.9 mg/l (4.6 mg/kg daily). The behaviour of each mouse was examined by ethological procedures during 5 min social encounters with an untreated partner in an aversive and a less aversive situation, an unfamiliar neutral cage and the animals' home cage. The behaviour of each mouse also was monitored for 5 min in the light-dark box. In the acute studies, behavioural observations commenced at 30 min after the injection. In the light-dark box, propranolol, after acute administration, increased the number of transitions between the light and dark compartments and increased scanning in the light area but propranolol had no significant effect after subchronic administration. In the home cage, propranolol significantly increased social investigation during social encounters and reduced exploratory activity at all doses tested, after both acute and subchronic administration. In the neutral cage, propranolol, after acute administration, increased digging of the sawdust and decreased exploratory activity at both dose levels, while at the largest dose it also increased social investigation. In the neutral cage, propranolol, given by subchronic administration, increased aggressive behaviour as well as social investigation and digging of the sawdust at both dose levels, while reducing non-social exploratory activity. The largest dose of propranolol also increased investigation of the substrate. These results indicate that propranolol increased reactivity to normal environmental and social stimuli, in addition to its anxiolytic profile of behavioural effects.(ABSTRACT TRUNCATED AT 250 WORDS)Neuropharmacology 09/1992; 31(8):749-56. · 4.11 Impact Factor
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ABSTRACT: We investigated how repeated agonistic confrontations affect the hypnotic effect of pentobarbital (PB) in male mice, using a resident-intruder paradigm. PB concentrations in the cortex, midbrain and brainstem were determined. Agonistic confrontations were terminated after 10 or 20 attack bites, and were repeated for 5 consecutive days. Immediately after the last encounter, PB (55 mg/kg, IP) was administered to both resident and intruder mice. Compared to the control group, intruders exposed to 20 daily attack bites showed a significant prolongation of the latency to sleep and a shortening of the duration of sleeping time. At the stage of induction, no significant difference in brain PB levels was found between the defeated and control intruders. At the stage of recovery, however, the defeated intruders showed a significantly low level of PB in all brain areas. In contrast, attacking resident mice did not show any significant changes in either the hypnotic effect or regional brain concentration of PB. Because pretreatment with naloxone prior to daily agonistic confrontation antagonized the alteration in PB-induced hypnosis, it seems that endogenous opioid mechanisms may participate in this phenomenon. The present study indicates that susceptibility to a hypnotic drug can be altered by chronic social conflict experience.Psychopharmacology 12/1988; 97(1):30-34. · 4.06 Impact Factor