Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol

Abstract

Buspirone is renowned for its highly inconsistent effects in animal models of anxiety. In the present study, the effects of acute (0.63-5.0 mg/kg) and chronic (1.25-5.0 mg/kg, daily, 15 days) buspirone treatment on the behaviour of mice in the elevated plus-maze test were assessed using a recently developed ethological scoring method. On acute administration, a selective reduction in risk assessment behaviours was observed at 1.25 mg/kg; these mild anxiolytic-like effects were maintained at higher doses (2.5-5.0 mg/kg) which also reduced measures of general activity. Similar, though more potent, effects were observed with chronic administration; the lowest dose tested (1.25 mg/kg) reduced open arm entries and total stretch attend postures while higher doses profoundly reduced all major indices of anxiety (traditional and novel) and, concomitantly, suppressed total entries and rearing. Acute administration of haloperidol (0.0125-0.1 mg/kg) appeared to mimic the behavioural suppressant effects of buspirone without selectively affecting anxiety-related measures at any dose. It is suggested that the anti-anxiety and behavioural suppressant profile of buspirone may reflect combined action at 5-HT1A and D2 receptors, respectively. Results are discussed in relation to the utility of risk assessment as a sensitive index of anxiety in models based upon unconditioned behaviour.

The Gerbil Elevated Plus-Maze I Behavioral Characterization and Pharmacological Validation

“…However, the 3 mg/kg dose appeared to selectively increase percentage of open arm time without affecting locomotion, suggesting that, at least in the gerbil, this is an anxiolytic-like dose. These complex findings with buspirone are in accordance with the rat and mouse elevated plus-maze literature, that describes either anxiogenic-like, anxiolytic-like, and/or sedative effects following buspirone treatment (Pellow and File 1986;Moser 1989;Lee and Rodgers 1991;Cole and Rodgers 1994;Cao and Rodgers 1997;Collinson and Dawson 1997). Overall, the gerbil elevated plusmaze appeared to have good predictive validity for detecting the anxiolytic-like effects of the benzodiazepine class of drugs.…”

“…However, the anxiolytic-like effects of buspirone at doses of 10 and 30 mg/kg were also accompanied by effects on locomotion, making interpretation of the data difficult, and suggesting that the effects of the 10 and 30 mg/kg doses of buspirone on the anxiolytic measures may be due to sedation, rather than anxiolysis (see Cole and Rodgers 1994). However, the 3 mg/kg dose appeared to selectively increase percentage of open arm time without affecting locomotion, suggesting that, at least in the gerbil, this is an anxiolytic-like dose.…”

Autonomic Changes Associated with Enhanced Anxiety in 5-HT1A Receptor Knockout Mice

“…Together with the observed tachycardia and hyperthermia, the increased burying and stretched approach postures are indicative for an enhanced fear/anxiety response in KO mice. Moreover, burying behavior and stretched approach postures have been shown to be sensitive to treatment with known anxiolytics, such as benzodiazepines (Cole and Rodgers 1993) and partial and full 5-HT 1A receptor agonists (De Boer et al 1991;Cole and Rodgers 1994;Rodgers et al 1994).…”

Central injections of nocistatin or its C‐terminal hexapeptide exert anxiogenic‐like effect on behaviour of mice in the plus‐maze test

“…an exploratory forward head/shoulder movement over the side an open arm of the maze directed down towards the¯oor) and protected stretch-attend postures (i.e. when animal stretches forward and retracts to original position without actually walking forward, a behaviour which occurs in or from the relative security of the closed arms or central platform of the maze) were also recorded (Cole & Rodgers, 1994).…”