Aspects of monoamine involvement in some aversively-motivated behaviours

Abstract

A study has been made of drugs acting at α -adrenoceptors and 5-HT receptors in some aversively-motivated behaviours (AMB). An elevated X-maze was used as a model of anxiety and was validated by investigating the effects of known anxiolytic and putative anxiogenic agents. In this model the α₂ -adrenoceptor agonists had an anxiolytic-like effect, whereas the antagonists appeared to be anxiogenic. The αˌ-adrenoceptor agonists as well as the 5-HT receptor agonist quipazine also had anxiogenic-like activity in this model and the αˌ-adrenoceptor antagonist prazosin and the 5-HT receptor antagonist ketanserin had anxiolytic-like effects. These results were confirmed by examining the effects of the agents on the Geller-Seifter conflict test - a widely accepted test for anxiety.These latter results not only provided evidence for the involvement of noradrenergic and serotonergic systems in these AMB, but also validated the X-maze as a reliable and rapid test for examining such behaviour. Evidence from behavioural interaction studies have suggested that the effect of α-adrenoceptor ligands in these models is not modulated by 5-HT receptors. Conversely, α-adrenoceptors do not appear to modulate the behavioural effects of the 5-HT receptor ligands. Biochemical determinations of 5-hydroxytryptamine (5-HT)and its metabolite 5-hydroxy-indole acetic acid (5-HIAA) in various brain regions after drug administration have shown that all these agents modify serotonergic activity. The importance of these changes have been discussed with special reference to studies that have investigated biochemical and behavioural interactions between anxiolytics and serotonergic systems - a field which appears to be under much controversy. Bilateral lesions of the locus coeruleus (L.C.)did not affect exploratory behaviour in the X-maze. The effect of α - adrenoceptors and 5-HT receptor ligands as well as diazepam and drenocorticotrophic hormone (ACTH)on conflict behaviour in L.C. lesioned animals was no different from sham-operated controls suggesting that the L.C. is not involved in these AMBs.