Ethopharmacological studies of the effects of β-carbolines and benzodiazepines on murine aggression

Abstract

The behavioral profiles generated by a benzodiazepine (BDZ) agonist (diazepam), an “inverse” agonist (β‐carboline‐3‐carboxylate ethyl ester, βC‐3‐CEE), and dihydro‐(DHβCs) and tetrahydro‐β‐carbolines (THβCs) were investigated on aggressive isolated mice using a computerized ethopharmacological technique. Augmentation of intraspecific sociability with a concurrent reduction of aggression are characteristic features of diazepam's effects, whereas βC‐3‐CEE exerts the opposite effects. βC‐3‐CEE countered the prosocial activity of diazepam and had intrinsic activities on intraspecific behaviour. Some DHβCs (harmalol and 6‐methoxy‐harmalan) and THβCs (1‐methyl‐6‐hydroxy‐THβC and tetrahydronorharmane) may exacerbate aggression at low (BDZ‐negative) doses (1 mg/kg), and inhibit such behavior at higher (serotonin‐positive) doses (10‐15 mg/kg). The ethological profiles of DHβCs were different from the profiles of THβCs. Differences in ethological profiles of βC‐3‐CEE, DHβCs, and THβCs seem to reflect the neurochemical (mainly BDZ‐and serotonergic) properties of these substances.

The GABAergic effect of low doses of lorazepam on social behavior

“…In the past few decades, the effects of benzodiazepines on aggression have been investigated in numerous pharmacological studies [Christmas and Maxwell, 1970;Cilia and Piper, 1997;Da Vanzo et al, 1966;Krsiak, 1979;Krsiak et al, 1981;Mos and Olivier, 1989;Pabis and Stanislav, 1996;Parmigiani et al, 1998;Poshivalov et al, 1987;Vale and Montgomery, 1997], but, on the whole, it could be said that there is no complete agreement as to their action on this behavior. Classically, decreases in aggression have been reported as a consequence of treatment with these drugs, although several researchers have reported increases, naming them "benzodiazepines' paradoxical effect" [Cutler et al, 1997;Feldman, 1986;Weerts and Miczek, 1996;Weisman et al, 1998].…”