Modulation by central postsynaptic alpha 2-adrenoceptors of the jaw-opening reflex induced by orofacial stimulation in rats.

1. The modulation by alpha 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 micrograms 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 (ED50 = 13.9 micrograms kg-1). 3. Pretreatment with the alpha 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 micrograms 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 alpha 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 (ED50 value decreased to 6.8 micrograms kg-1) without a significant change of maximum inhibitory effect. 5. Increasing doses of amphetamine (0.1-3000 micrograms kg-1, i.v.) caused a dose-related, but partial, inhibition of the OF-JOR (ED50 = 135 micrograms kg-1; Emax = 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 alpha-methyl-p-tyrosine (150mg 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 microgkg-1, i.v.) also reduced the OF-JOR in a dose-dependent manner (ED50 value about 325 microg kg-1) but, in contrast to clonidine, it failed to inhibit the reflex fully (Emax = 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 (ED50 value decreased to 4.2 microg 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 alpha2-adrenoceptors. It is suggested that this functional response represents a simple and useful in vivo model for studying various regulatory mechanisms of central alpha2-adrenoceptors.