The effect of central and systemic injection of the 5-HT1A receptor agonist 8-OHDPAT and the 5-HT1A receptor antagonist WAY100635 on periaqueductal grey-induced defence behaviour

Abstract

The effects of the selective 5-HT_1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT) and the selective 5-HT_1A antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperzinyl]ethyl]-N-(pyridinyl) cyclohexanecarboxa mide trichloride (WAY100635) on periaqueductal grey (PAG)-stimulated defence behaviour were tested in the rat. Microinjection of the excitatory amino acid, D, L-homocysteic acid (DLH) into the dorsal region of the PAG produced overt aversive behaviour characteristic of the defence response, consisting of explosive motor behaviours which were quantified in terms of their duration and the number of arena revolutions and jumps made by the animal. Intra-PAG pre-treatment with 8-OHDPAT (3, 10 and 25 nmol in 250 nl) 10 min before DLH stimulation significantly attenuated the defence behaviour. This could be reversed by peripheral application of WAY100635 (0.1 mg/kg). In contrast, peripheral 8-OHDPAT (0.03, 0.1 and 0.3 mg/kg) produced a significant potentiation of the DLH response which could also be blocked by peripheral WAY100635. When WAY100635 (10 nmol in 250 nl) alone was given into the PAG a significant increase in DLH induced behaviours was observed whereas peripherally applied WAY100635 (0.1 mg/kg) was without effect. These data support previous findings which indicate that serotonergic modulation of aversive behaviours such as defence can be mediated by 5-HT _1A receptors. Furthermore there is evidence to indicate a differential involvement of pre- and post synaptic 5-HT_1A receptors.