Evidence that central 5-hydroxytryptaminergic neurones are involved in the anxiolytic activity of buspirone.
1. A two-compartment exploratory test was used to assess the role of central 5-hydroxytryptaminergic neurones in the anxiolytic activity of buspirone in rats. 2. Buspirone 0.1 mg kg-1, administered subcutaneously 15 min before testing, significantly increased black-white transitions (BWT) in control rats but had no effect in animals injected intracerebroventricularly one week before with 150 micrograms 5,7-dihydroxytryptamine (in 20 microliters). 3. Infusion of buspirone in the median raphe (but not in the dorsal raphe) significantly enhanced BWT, at doses from 1 micrograms to 10 micrograms (in 0.5 microliters). Buspirone 5 and 10 micrograms, but not 1 microgram, administered in the median raphe, significantly enhanced motor activity of rats during the first 10 min of testing in the activity cages. 4. The effect on BWT of 5 micrograms buspirone in the median raphe was completely antagonized in animals which had received either 5,7-dihydroxytryptamine intraventricularly, 150 micrograms (in 20 microliters), one week before or an infusion of 0.1 microgram (in 0.5 microliter) (-)-propranolol in the same area 5 min before. (-)-Propranolol infused in the median raphe did not modify the effect of buspirone on locomotion. 5. Infusion of 5 micrograms buspirone (in 0.5 microliter) in the median raphe significantly enhanced punished responses in a conflict test with no effect on unpunished responding. Buspirone infused in the dorsal raphe had no effect on punished or unpunished responding over a wide dose range. 6. The results indicate that at the relatively low dose used in the present study buspirone produces an anxiolytic effect by acting on central 5-hydroxytryptaminergic neurones. It is likely that activation of 5-hydroxytryptamine1A-receptors in the median raphe is involved.
Carli
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Prontera
C
C
Samanin
R
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents; D002065:Buspirone / Q000494:pharmacology*; D003220:Conflict, Psychological; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000502:physiology*; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone