title: Effects of diazepam on behavioural and antinociceptive responses to the elevated plus-maze in male mice depend upon treatment regimen and prior maze experience.
abstract: Recent studies have shown that brief exposure to an elevated plus-maze (EPM) produces non-opioid antinociception in male mice. The present experiments were designed to assess the effects of diazepam on this phenomenon. When acutely administered, low doses (0.5-1.0 mg/kg) of diazepam failed to produce an anxiolytic profile and exerted rather inconsistent effects on EPM-induced elevations in tail-flick latencies. In EPM-experienced mice, chronic treatment with higher doses of diazepam (2-4 mg/kg, 8 days) produced a weak anxiolytic action and inhibited the early phase of EPM antinociception only. However, in EPM-naive mice, 8-day diazepam pretreatment exerted a marked anxiolytic effect and completely eliminated the antinociceptive response to the maze. Together, these data support the view that anxiety is a key factor in certain forms of adaptive pain inhibition and suggest a possible mediational role for benzodiazepine receptors. Our findings also show that prior exposure to the EPM, rather than chronic handling/injection, greatly reduces the anti-anxiety effect of diazepam. Furthermore, since re-exposure to the maze, per se, decreased time spent on the open arms and central platform, a shift in behavioural baseline ("retest anxiogenesis") may have contributed to the weak behavioural effects of diazepam in test-experienced animals. Importantly, as chronic treatment with diazepam did not influence this anxiogenic-like retest profile, our data suggest that a single prior experience of the EPM may radically alter the nature of the anxiety reaction provoked by this test.
authors.affiliation: Department of Psychology, University of Leeds, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Rodgers
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: J K
authors.initials: JK
authors.lastname: Shepherd
mesh_terms: D000698:Analgesia; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010147:Pain Measurement
chemical_list: D003975:Diazepam