INVOLVEMENT OF NITRIC-OXIDE AND SEROTONIN IN MODULATION OF ANTINOCICEPTION AND PRESSOR-RESPONSES EVOKED BY STIMULATION IN THE DORSOLATERAL REGION OF THE PERIAQUEDUCTAL GRAY-MATTER IN THE RAT

In rats anaesthetized with alphaxalone/alphadolone, electrical stimula tion in the periaqueductal gray matter in the region lying lateral and dorsolateral to the aqueduct produced a presser response and an incre ase in the latency of the tail flick response to noxious heal applied to the tail. The antinociception and the presser response were signifi cantly attenuated following microinjection of 15 nmol 5-hydroxytryptam ine at the site of stimulation in the periaqueductal gray matter. Micr oinjection of an equal volume of 165 mM saline had no effect. The inhi bitory effects of 5-hydroxytryptamine were blocked by prior intracereb roventricular administration of 100 mu g of the nitric oxide synthase inhibitor L-nitroarginine methyl ester. Neither 5-hydroxytryptamine or L-nitroarginine methyl ester had any effect on resting arterial press ure or on the baseline latency of the tail flick reflex. It is suggest ed that the inhibitory effects of 5-hydroxytryptamine in the dorsolate ral periaqueductal gray matter are normally dependent on the functiona l integrity of local nitric oxide synthase-containing interneurons. Ni tric oxide may act in association with 5-hydroxytryptamine to control the excitability of the aversive system in the midbrain.