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 microg, -10 min) into the DR or MR, respectively, produced a significant reversal of haloperidol-induced CAT. Lower doses (5 or 25 microg) 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 microg) 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 serotonergic 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.
Wadenberg
M L
ML
Department of Psychiatry, Scott and White Clinic and Memorial Hospital, Scott Sherwood and Brindley Foundation, Temple, TX 76508, USA. wadenbergm@cs.clarke-inst.on.ca
Young
K A
KA
Richter
J T
JT
Hicks
P B
PB
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000633:toxicity*; D006220:Haloperidol / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology
D018492:Dopamine Antagonists; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012701:Serotonin; D012965:Sodium Chloride; D006220:Haloperidol; C031466:amiflamine; D004298:Dopamine