MODULATION BY CENTRAL POSTSYNAPTIC ALPHA(2)-ADRENOCEPTORS OF THE JAW-OPENING REFLEX INDUCED BY OROFACIAL STIMULATION IN RATS

1 The modulation by alpha2-adrenoceptors of the jaw-opening reflex (di gastric electromyographic responses) elicited by orofacial electrical stimulation (OF-JOR) in pentobarbitone anaesthetized rats was investig ated. 2 Increasing doses of clonidine (0.1-1000 mug kg-1, i.v.) reduce d, in a dose-dependent manner until abolition, the amplitude and durat ion of the OF-JOR and increased the latency to onset. The sum of ampli tudes of the reflex was the most sensitive parameter to the inhibitory effects of clonidine (ED50 = 13.9 mug kg-1). 3 Pretreatment with the alpha2-adrenoceptor antagonist, idazoxan (0.03-1 mg kg-1, i.v.), cause d a dose-dependent shift (1.5 to 37 fold) to the right of the dose-res ponse curve for clonidine without significant change of maximum inhibi tory effect, in a manner compatible with competitive antagonism (ED50B = 29.0 mug kg-1). Pretreatment with yohimbine (0.3 mg kg-1, i.v.) als o antagonized the inhibitory effect of clonidine on the OF-JOR. In con trast, the alpha2-adrenoceptor antagonist ARC-239 (0.3 mg kg-1, i.v.) did not antagonize the effect of clonidine on the reflex. 4 In rats pr etreated with reserpine (5 mg kg-1, s.c., 18 h) the OF-JOR was not mod ified, but the potency of clonidine in inhibiting the reflex was poten tiated (ED50 value decreased to 6.8 mug kg-1) without a significant ch ange of maximum inhibitory effect. 5 Increasing doses of amphetamine ( 0.1 - 3000 mug kg- 1, i.v.) caused a dose-related, but partial, inhibi tion of the OF-JOR (ED50 = 135 mug kg-1; E(max) = 67%). Pretreatment w ith idazoxan (0.1 mg kg-1, i.v.) induced a nine fold shift to the righ t of the dose-response curve for amphetamine, while treatment with the depleting drug alpha-methyl-p-tyrosine (150 mg kg-1 daily, i.p., for 14 days) abolished the inhibitory effect of this indirect adrenoceptor agonist on the OF-JOR. 6 Morphine (0.1-3000 mug kg-1, i.v.) also redu ced the OF-JOR in a dose-dependent manner (ED50 value about 325 mug kg -1) but, in contrast to clonidine, it failed to inhibit the reflex ful ly (E(max) = 48%). As expected, pretreatment with the opioid antagonis t naloxone (1 mg kg-1, i.v.) abolished the inhibitory effect of morphi ne on the OF-JOR, while it did not alter that of clonidine. 7 Chronic, but not acute, pretreatment with idazoxan (3 mg kg-1 daily, i.p. for 14 days) led to a marked potentiation of the inhibitory effect of clon idine on the OF-JOR (ED50 value decreased to 4.2 mug kg-1), without a significant change of maximum inhibitory effect. 8 Together the result s indicate that clonidine evokes a potent inhibition of the OF-JOR in rats through the activation of postsynaptic alpha2-adrenoceptors. It i s suggested that this functional response represents a simple and usef ul in vivo model for studying various regulatory mechanisms of central alpha2-adrenoceptors.