Modulation by central postsynaptic α 2 ‐adrenoceptors of the jaw‐opening reflex induced by orofacial stimulation in rats

1 The modulation by α 2 ‐adrenoceptors of the jaw‐opening reflex (digastric electromyographic responses) elicited by orofacial electrical stimulation (OF‐JOR) in pentobarbitone anaesthetized rats was investigated. 2 Increasing doses of clonidine (0.1–1000 μg kg −1 , i.v.) reduced, in a dose‐dependent manner until abolition, the amplitude and duration of the OF‐JOR and increased the latency to onset. The sum of amplitudes of the reflex was the most sensitive parameter to the inhibitory effects of clonidine (ED 50 = 13.9 μg kg −1 ). 3 Pretreatment with the α 2 ‐adrenoceptor antagonist, idazoxan (0.03–1 mg kg −1 , i.v.), caused a dose‐dependent shift (1.5 to 37 fold) to the right of the dose‐response curve for clonidine without significant change of maximum inhibitory effect, in a manner compatible with competitive antagonism (ED50B = 29.0 μg kg −1 ). Pretreatment with yohimbine (0.3 mg kg −1 , i.v.) also antagonized the inhibitory effect of clonidine on the OF‐JOR. In contrast, the α 2 ‐adrenoceptor antagonist ARC‐239 (0.3 mg kg −1 , i.v.) did not antagonize the effect of clonidine on the reflex. 4 In rats pretreated with reserpine (5 mg kg −1 , s.c., 18 h) the OF‐JOR was not modified, but the potency of clonidine in inhibiting the reflex was potentiated (ED 50 value decreased to 6.8 μg kg −1 ) without a significant change of maximum inhibitory effect. 5 Increasing doses of amphetamine (0.1–3000 μg kg −1 , i.v.) caused a dose‐related, but partial, inhibition of the OF‐JOR (IC 50 = 135 μg kg −1 ; E max = 67%). Pretreatment with idazoxan (0.1 mg kg −1 , i.v.) induced a nine fold shift to the right of the dose‐response curve for amphetamine, while treatment with the depleting drug α‐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 μg kg −1 , i.v.) also reduced the OF‐JOR in a dose‐dependent manner (ED 50 value about 325 μg kg −1 ) but, in contrast to clonidine, it failed to inhibit the reflex fully ( E max = 48%). As expected, pretreatment with the opioid antagonist naloxone (1 mg kg −1 , i.v.) abolished the inhibitory effect of morphine 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 clonidine on the OF‐JOR (ED 50 value decreased to 4.2 μg kg −1 ), without a significant change of maximum inhibitory effect. 8 Together the results indicate that clonidine evokes a potent inhibition of the OF‐JOR in rats through the activation of postsynaptic α 2 ‐adrenoceptors. It is suggested that this functional response represents a simple and useful in vivo model for studying various regulatory mechanisms of central α 2 ‐adrenoceptors.