Anxiogenic-like effects of fluprazine and eltoprazine in the mouse elevated plus-maze: profile comparisons with 8-OH-DPAT, CGS 12066B, TFMPP and mCPP.
It has recently been proposed that the "serenic" (antiaggressive) agents, fluprazine and eltoprazine, may enhance fear/anxiety reactions in laboratory rodents. In the present study, the influence of these compounds (1.25-10.0mg/kg) on anxiety-related behaviour in male mice was examined in the elevated plus-maze test. For comparative purposes, the effects of 8-OH-DPAT (0.01-1.0mg/kg) CGS 12066B (1.25-10mg/kg), TFMPP (0.63-5.0mg/kg) and mCPP (0.5-4.0mg/kg) were also assessed. Behavioural analysis incorporated not only traditional parameters but also several novel measures of defensive behaviour (i.e. "risk assessment"). The selective 5-HT(1A) agonist 8-OH-DPAT produced effects only at 1.0mg/kg, with evidence of an anxiolytic/sedative action at this dose. In the absence of other behavioural changes, CGS 12066B (a selective 5-HT(1B) agonist) caused a preferential and dose-dependent (2.5-10.0mg/kg) stimulation of closed arm entries, an effect also seen with low doses of TFMPP (0.63mg/kg) and the serenics (1.25-2.5mg/kg). In addition, both TFMPP and mCPP (5-HT(1C/1B) agonists) induced dose dependent anxiogenic-like effects over the dose ranges tested, with the most pronounced changes observed on measures of risk assessment. The profiles of fluprazine and eltoprazine on plus-maze behaviour were not only similar to one another but, on most parameters, were also remarkably like those observed with TFMPP and mCPP. These data question the behavioural selectivity of the serenics and further support the proposal that these compounds may potentiate anxiety. Findings are discussed in relation to underlying receptor mechanisms, and the utility of a more ethological approach to the analysis of behaviour on the elevated plus-maze.
Department of Psychology, University of Leeds, Leeds LS2 9JT, UK.
R.J.
RJ
Rodgers
J.C.
JC
Cole
M.R.
MR
Cobain
P.
P
Daly
P.J.
PJ
Doran
J.R.
JR
Eells
P.
P
Wallis