The effects of alpha 2-adrenoceptor antagonists on the inhibition of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head shakes by 5-HT1A receptor agonists in the mouse.

1. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), gepirone, buspirone and ipsapirone dose-dependently antagonized the head-shakes induced by 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane hydrochloride (DOI) (1.0 mg kg-1) in mice, when these agents were given i.p. 10 min beforehand. 2. para-Chlorophenylalanine (pCPA) abolished the effect of 8-OH-DPAT (0.1 mg kg-1) and of buspirone (1.0 mg kg-1). (+/-)-Pindolol (5.0 mg kg-1) also antagonized the effect of 8-OH-DPAT (0.1 mg kg-1). 3. The alpha 2-adrenoceptor antagonists, RX811059 (1.0 mg kg-1), idazoxan (0.5 mg kg-1), yohimbine (1.0 mg kg-1) and 1-(2-pyrimidinyl)-piperazine (1-PP) (2.0 mg kg-1) i.p. prevented the antagonistic effect of 8-OH-DPAT (0.1 mg kg-1) on DOI-head-shakes. 4. Orally-administered buspirone, given 60 min beforehand, only reduced DOI-head-shakes at doses of 60 mg kg-1 and above. However, when buspirone (1.0 mg kg-1) was administered orally twice daily for 21 days, DOI-head-shakes were significantly reduced when tested 60 min after the first daily dose on days 5, 12 and 21 and 48 h after withdrawal. 5. A single oral dose of buspirone (1.0 mg kg-1) strongly antagonized DOI-head-shakes when given 24 h after the last of 4 daily doses of 1-PP (2.0 mg kg-1, p.o.) but had no effect on DOI-head-shakes 24 h after the last of 4 daily doses of water (p.o.). 6. A single oral dose of 1-PP (2.0 mg kg-1) abolished the inhibitory effect of i.p. buspirone(1.0 mg kg-1) on DOI-head-shakes in mice which had received water (p.o.) daily on the 4 previous days but not in mice which had received 1-PP (2.0mg kg-1, p.o.) on these days.7. The ability of 5-HT1A receptor agonists to antagonize DOI-head-shakes may be due to an effect at presynaptic 5-HT receptors. It is suggested that 1-PP, formed from buspirone, may act at a2-adrenoceptors to prevent acutely administered oral buspirone from antagonizing DOI-head shakes, but that tolerance occurs to this effect of I-PP, thus revealing the inhibitory effect of buspirone when the latter is given repeatedly.