Neuroanatomical sites of action of 5-HT3 receptor agonist and antagonists for alteration of aversive behaviour in the mouse.
1. The cerebral topography of the action of diazepam and the action of the 5-hydroxytryptamine 5-HT3 receptor antagonists GR38032F and ICS 205-930 in attenuating an aversive response was studied in the mouse. 2. Mice which had been cannulated to allow drug injection into the dorsal and median raphe nuclei, the amygdala, nucleus accumbens or caudate-putamen were placed in a two compartment black (dimly illuminated) and white (brightly illuminated) test box. Measurements were made of the time spent, rearing and line crossings in the two sections and the latency of initial movement from the white to the black area. 3. The injection of diazepam (0.1-10 ng), GR38032F (0.01-1.0 ng) and ICS 205-930 (1.0-10 ng) into the dorsal raphe nucleus and amygdala, and the injection of diazepam (0.1-10 ng) into the median raphe nucleus, reduced an aversive response to the brightly illuminated white area, delaying the initial movement into the black section and increasing the time spent, rearings and line crossings in the white area. Concomitantly such activities were decreased in the black section. 4. The injection of the 5-HT3 agonist 2-methyl-5-hydroxytryptamine (0.1-10 ng) into the dorsal raphe nucleus and amygdala caused the opposite response, decreasing the time taken to move into the black section and increasing the time spent, rearings and line crossings in the black section, decreasing such activities in the white area. 5. The 5-HT3 agonist and antagonists showed little or no effect following injection into the median raphe nucleus and there were no changes in exploratory behaviour following their injection, or injection of diazepam, into the nucleus accumbens or caudate-putamen. 6. It is concluded that in the mouse the cerebral topography of action of GR38032F and ICS 205-930 in attenuating an aversive response follows that of diazepam in the dorsal raphe nucleus and amygdala but that diazepam may have additional effects mediated via the median raphe nucleus.
Costall
B
B
Postgraduate School of Studies in Pharmacology, University of Bradford.
Kelly
M E
ME
Naylor
R J
RJ
Onaivi
E S
ES
Tyers
M B
MB
D000818:Animals; D001921:Brain / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D017294:Ondansetron; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000077526:Tropisetron
D007093:Imidazoles; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017294:Ondansetron; D000077526:Tropisetron; D003975:Diazepam