Modulation by central postsynaptic α₂‐adrenoceptors of the jaw‐opening reflex induced by orofacial stimulation in rats

Abstract

1The modulation by x2-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 tgkg-', 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 =13.91Lg kg-').3 Pretreatment with the a2-adrenoceptor antagonist, idazoxan (0.03-1 mg kg-', i.v.), caused a dosedependent 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 jig kg-'). Pretreatment with yohimbine (0.3 mg kg-', i.v.) also antagonized the inhibitory effect of clonidine on the OF-JOR. In contrast, the M2-adrenoceptor antagonist ARC-239 (0.3 mg kg-', i.v.) did not antagonize the effect of clonidine on the reflex. 4 In rats pretreated with reserpine (5 mg kg-', 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 jg kg-') without a significant change of maximum inhibitory effect. induced a nine fold shift to the right of the dose-response curve for amphetamine, while treatment with the depleting drug a-methyl-p-tyrosine (150mg kg' daily, i.p., for 14 days) abolished the inhibitory effect of this indirect adrenoceptor agonist on the OF-JOR.6 Morphine (0.1-3000ftgkg-', i.v.) also reduced the OF-JOR in a dose-dependent manner (ED50 value about 325,ug kg-') but, in contrast to clonidine, it failed to inhibit the reflex fully (Em,, = 48%).As expected, pretreatment with the opioid antagonist naloxone (1 mg kg-', 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' 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 jig kg-'), 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 M2-adrenoceptors. It is suggested that this functional response represents a simple and useful in vivo model for studying various regulatory mechanisms of central 2-adrenoceptors.

Repeated tail pinch leads to desensitization of postsynaptic α 2 -adrenoceptors which modulate the jaw-opening reflex in the rat

“…This could be due to a certain state of activation of the postsynaptic a 2 -adrenoceptors which regulate the OF-JOR elicited by the endogenous NE released during the Þrst minutes after exposure to this stressor. In this context, we have previously observed a dose-dependent reduction of the basal amplitude of the reßex after amphetamineinduced endogenous NE release (García-Vallejo et al 1994). More speciÞcally, after acute tail pinch, an immediate enhancement of NE extracellular levels in hippocampus, amygdala, prefrontal cortex and hypothalamus has been reported, although the levels rapidly returned to their basal values (Kálen et al 1989;Tanaka et al 1991;Finlay et al 1995;Shibasaki et al 1995).…”

“…DMC 25, Medelec Limited, Survey, UK). The methodology described by García-Vallejo et al (1994), with minor modiÞcations, was followed for both stimulation and recordings. In all experiments, two initial recordings were obtained in the absence of the drug to assess the basal value of the OF-JOR.…”

“…It can be assumed that stress-induced changes in central a 2 -adrenoceptors constitute a molecular basis for behavioural and psychological changes in stressed individuals (McEwen and Sapolsky 1995), and in vivo functional studies in animals can contribute to a better understanding of how stress modiÞes the sensitivity of these receptors (Cancela et al 1988;Pavcovich et al 1990;Nisenbaum and Abercrombie 1993;Fulford et al 1994). In this context, the evaluation of clonidine-induced inhibition of the jaw-opening reßex (JOR) has been suggested as a useful in vivo model for the study of the regulatory mechanisms of central a 2 -adrenoceptors in the rat (García-Vallejo et al 1994). …”

“…The activation of postsynaptic central a 2 -adrenoceptors in the rat by systemic administration of clonidine, an a 2 -adrenoceptor agonist, induces a relevant dose-dependent inhibition of the JOR until abolition (García-Vallejo et al 1994).…”

Effects of 3,4‐methylenedioxymethamphetamine (‘Ecstasy’) on the jaw‐opening reflex and on the α2‐adrenoceptors which regulate this reflex in the anesthetized rat

“…For the evaluation of the effects of the drugs on the α 2 ‐adrenoceptors, the parameter sum of amplitudes (Σ amplitude) was evaluated as, in a former study, it had been observed that this is the most sensitive for evaluating the inhibitory effect of clonidine and presents the best correlation coefficient (22). The Σ amplitude was defined as the arithmetical addition of each peak‐to‐peak value of every wave that formed the configuration of the reflex.…”