The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat

The centrally active 5-HT receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has a high affinity for the 5-HT1A subtype of the 5-HT1 recognition site in cerebral membranes and, in the rat, induces most aspects of the '5-HT behavioural syndrome' including hyperlocomotion, head weaving, a flat body posture and reciprocal forepaw treading. The mechanism of action of 8-OH-DPAT in producing these effects has been investigated. Consistent with an involvement of catecholaminergic neurons, reserpine dose-dependently reduced hyperlocomotion and head weaving, and most components of the syndrome were reduced by prazosin, haloperidol and sulpiride. However, reserpine did not block forepaw treading or the flat body posture, allowing pharmacological analysis of these behaviours in the absence of intact monoaminergic systems. Under these circumstances blockade by the selective 5-HT2 receptor antagonist, ketanserin, and by haloperidol was not seen, and only the flat body posture was significantly reduced by prazosin, rendering a key role for 5-HT2 receptors, alpha 1-adrenoceptors and dopamine receptors unlikely. In contrast, both behaviours in the reserpinised rat were inhibited stereospecifically by pindolol and by spiperone, which interact with 5-HT1 and 5-HT1A recognition sites. The residual behavioural effects of 8-OH-DPAT in reserpinised rats may, therefore, reflect the consequences of stimulation of the putative 5-HT1A receptor.