DIFFERENT FUNCTIONS OF SPINAL 5-HT(1A) AND 5-HT(2) RECEPTOR SUBTYPES IN MODULATING BEHAVIOR INDUCED BY EXCITATORY AMINO-ACID RECEPTOR AGONISTS IN MICE

The modulating effects of 5-HT1A and 5-HT2 receptor agonists on behaviour induced by spinal excitatory amino acid (EAA) agonists were examined. Intrathecal (i.th.) administration of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) produce a behavioural syndrome of caudally directed biting and scratching. Serotonin (5-HT) agonists were coadministered with either NMDA or AMPA, and changes in EAA-induced behaviour were scored. All drugs were administered i.th. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (15-60 nmol) reduced both NMDA (0.25 nmol) and AMPA (0.06 nmol) induced behaviour in a dose-dependent manner, and preadministration of the 5-HT1A receptor antagonist, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)bytyl]piperazine hydrobromide (NAN-190) (20 nmol) reversed this effect. The administration of the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.7-28 nmol) produced a dose-dependent behavioural syndrome similar to the EAA agonists. This was reversed by preadministration of ritanserin (10 nmol), a 5-HT2 antagonist. When DOI was coadministered with NMDA (0.25 nmol) or AMPA (0.06 nmol) there was an increase in the behaviour recorded and this effect was antagonised by ritanserin. The results of this study implicate that in the spinal cord subtypes of 5-HT receptors have different effects on modulation of behaviour induced by activation of the NMDA or the AMPA receptors; the activated 5-HT1A receptors have an inhibitory effect whereas activation of the 5-HT2 receptors enhance the induced behaviour.