Effects of local application of 5-hydroxytryptamine into the dorsal or median raphe nuclei on haloperidol-induced catalepsy in the rat

The effects of local application of the endogenous brain neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) into the dorsal (DR) or median (MR) raphe nuclei on haloperidol-induced catalepsy (CAT) in rats were studied. Local application of 5-HT (40 mu g, - 10 min) into the DR or MR, respectively, produced a significant reversal of haloperidol-induced CAT. Lower doses (5 or 25 mu g) of 5-HT were ineffective. Compared to previous studies using the selective 5-HT1A receptor agonist 8-OH-DPAT, the non-selective endogenous serotonin receptor agonist 5-HT was significantly less potent in this paradigm. Furthermore, the observed anticataleptic effect of 5-HT was seen following injections into both DR or MR nuclei. The reversal of CAT by local application of 5-HT (40 mu g) into the DR was significant also at 70 min after 5-HT administration, with the same tendency for 5-HT injections into the MR. At this time interval, other serotonegic behavioral symptoms like head twitches and wet-dog shakes also emerged. The early reversal of CAT by local 5-HT administration into the MR is in all probability mediated via stimulation of 5-HT1A autoreceptors on raphe serotonergic cell bodies. The reversal of CAT following 5-HT injections into the DR might alternatively be mediated via functional mechanisms other than stimulation of 5-HT1A autoreceptors. The anticataleptic effects observed at the later observation time could be due to stimulation of postsynaptic 5-HT2 receptors following diffusion of 5-HT into 5-HT2 receptor rich areas of the brain. (C) 1999 Elsevier Science Ltd. All rights reserved.