Orienting and defensive behaviors elicited by superior colliculus stimulation in rats: effects of 5-HT depletion, uptake inhibition, and direct midbrain or frontal cortex application.

Electrical or chemical stimulation of the superior colliculus (SC) in rats produces orienting and defensive responses. Defensive behaviors are modulated by serotonin (5-hydroxytryptamine, 5-HT), and serotonergic fibers provide a dense innervation of the SC. Here, we examined the role of 5-HT in modulating the behavioral responses of rats elicited by electrical SC stimulation. Low-intensity (107+/-12 microA) stimulation of the SC elicited orienting head movements, while higher intensities (204+/-20 microA) produced running and jumping responses. Treatment with the 5-HT depletor p-chlorophenylalanine (300 mg/kg/day x 3, i.p.) lowered current thresholds to elicit orienting and running by 40 and 21%, respectively. Conversely, concurrent administration of the 5-HT uptake inhibitor fluoxetine (10 mg/kg, i.p.) and the 5-HT(1A) receptor antagonist WAY 100635 (0.5 mg/kg, s.c.) increased threshold currents to produce head and running movements by 41 and 18%, respectively. We investigated the anatomical substrate of this inhibitory effect of 5-HT with intracerebral 5-HT application by means of reverse microdialysis. Application of 5-HT (1-50 mM) into the midbrain immediately adjacent to the SC stimulation electrode resulted in a pronounced (approximately four-fold for 50 mM 5-HT) dose- and time-dependent increase in stimulation thresholds to elicit head movements. Application of 5-HT into the frontal cortex (up to 100 mM) had no significant effect on SC-evoked behavioral responses. These results show that 5-HT exerts an inhibitory influence over orienting and defensive behaviors initiated in the mammalian SC. It appears that this inhibitory effect is mediated, to a large extent, by a direct action of 5-HT at the level of the midbrain.