Occlusal disharmonies modulate central catecholaminergic activity in the rat.

Occlusal disharmonies have classically been thought to be involved in the etiopathogenesis of bruxism, as have, more recently, alterations in central neurotransmission, particularly dopaminergic neurotransmission. However, the connection between these two factors has still not been established. In this study, we assessed the effects of diverse occlusal disharmonies, maintained for either 1 day or 14 days, on neurochemical indices of dopaminergic and noradrenergic activity in the striatum, frontal cortex, and hypothalamus of the rat. The in vivo activity of tyrosine hydroxylase, determined as the accumulation of 3,4-dihydroxyphenylalanine (DOPA), 30 min after the administration of 3-hydroxybenzylhydrazine, a DOPA decarboxylase inhibitor, and dopamine and noradrenaline contents were quantified by high-performance liquid chromatography with electrochemical detection. The wearing of an acrylic cap on both lower incisors for 1 day induced a significant increase in DOPA accumulation in the regions analyzed, with parallel increases in dopamine levels in the hypothalamus and dopamine and noradrenaline in the frontal cortex. After the cap was maintained for 14 days, DOPA accumulation tended to return to control values, except in the left striatum, thereby causing an imbalance between hemispheres. In contrast, 1 or 14 days after the lower left and the upper right incisors were cut, less pronounced changes in catecholaminergic neurotransmission were found in the brain areas studied. Moreover, the cutting of one lower incisor did not modify either DOPA accumulation or dopamine and noradrenaline contents in the striatum or hypothalamus. These results provide experimental evidence of a modulation of central catecholaminergic neurotransmission by occlusal disharmonies, being dependent on the nature of the incisal alteration and on the time during which it was maintained.

A possible attenuation of stress-induced increases in striatal dopamine metabolism by the expression of non-functional masticatory activity in the rat.

It is thought that the expression of oral parafunctions may provide an outlet for stress or aggressiveness in man. Stress-induced increases in central noradrenergic neurotransmission are attenuated in rats which are allowed to bite during stress. Striatal dopaminergic neurotransmission is involved in the genesis of parafunctional oral movements in rodents. As tail pinch is the stressor which most clearly provokes non-functional masticatory activity (NFMA), and also increases striatal dopamine (DA) activity in rats, we investigated whether the expression of NFMA during tail pinch could modify the changes in striatal dopaminergic neurotransmission induced by this stressor. Rats were subjected to tail pinch for 5 min, and the duration of the NFMA displayed was recorded. As an index of dopaminergic activity, 3,4-dihydroxyphenylalanine (DOPA) accumulation and DA and 3,4-dihydroxyphenylacetic (DOPAC) contents in both striata were determined by high-performance liquid chromatography. Striatal DOPA accumulation was similarly increased in relation to control, both in rats which did and did not display NFMA during tail pinch. However, the increases in striatal DOPAC contents, reported 24 min after the stress session, were lower in animals which had displayed NFMA. These results provide further evidence in support of the assumption that the expression of parafunctional masticatory activity attenuates the effects of stress on central catecholaminergic neurotransmission.

Chronic variable stress induces supersensitivity of central alpha2-adrenoceptors which modulate the jaw-opening reflex in the rat.

In a previous study, we found that the sensitivity of central postsynaptic alpha2-adrenoceptors which modulate, in an inhibitory way, the activity of the jaw-opening reflex (JOR) is reduced after chronic repeated stress (tail pinch) in the rat. The aim of this study was to assess the effects of exposure to a chronic variable stress regime on these adrenoceptors. To do this, the digastric electromyographic responses elicited by orofacial electrical stimulation after the intravenous administration of cumulative doses (x3.3) of the alpha2-adrenoceptor agonist, clonidine (0.1-10000 microgram/kg), were recorded. As expected, in unmanipulated control rats, clonidine inhibited the reflex, in a dose-dependent manner, until abolition (ED50 = 17.3 +/- 2.2 microgram/kg). Single tail pinch did not significantly alter the ability of clonidine to abolish the reflex. However, chronic variable stress led to an enhancement of the inhibitory effect of clonidine on the amplitude of JOR, resulting in a shift to the left of the dose-response curve in comparison with that of the control group (ED50 was reduced by 37%, P = 0.032), without affecting either the estimated maximum effect for the agonist or the slope of the inhibitory function. This in vivo result indicates that chronic variable stress leads to an increased sensitivity of central alpha2-adrenoceptors which modulate JOR, in contrast to the desensitization of these adrenoceptors found after repeated exposure to the same stressor.

Repeated tail pinch leads to desensitization of postsynaptic alpha2-adrenoceptors which modulate the jaw-opening reflex in the rat.

There are few in vivo studies which have investigated the modulation of central postsynaptic alpha2-adrenoceptors functionality provoked by stress. We assessed in the rat the effects of either single or repeated tail pinch on clonidine-induced inhibition of the jaw-opening reflex (JOR) via activation of postsynaptic central alpha2-adrenoceptors. At the end of each experimental period, the progressive inhibition of the digastric electromyographic responses elicited by orofacial electrical stimulation after the i.v. administration of cumulative doses (x3.3) of clonidine (0.1-10000 microg/kg) was recorded. Single tail pinch did not significantly modify the ability of the agonist to inhibit the JOR, although there was a tendency to decrease the basal amplitude of the reflex (a 40% reduction) immediately after exposure to the single stressor. However, the dose-response curve for clonidine-induced inhibition of the JOR was clearly shifted to the right in rats exposed to repeated tail pinch (ED50 was increased by 152%, P < 0.0001) when compared with the unstressed control group, without affecting the slope of the inhibitory function and the estimated maximum effect for the agonist. These results show that repeated stress leads to a subsensitivity of the alpha2-adrenoceptors which modulate the JOR, suggesting the development of adaptive mechanisms in postsynaptic alpha2-adrenoceptors in response to stress.

Effects of dopaminergic drugs, occlusal disharmonies, and chronic stress on non-functional masticatory activity in the rat, assessed by incisal attrition.

Observational methods and the recording of nonspecific jaw movements or masticatory muscle activity have been used to evaluate oral parafunctional movements in animal models of bruxism. In this study, we have used a new approach in which the non-functional masticatory activity in the rat was assessed by the measurement of incisal attrition, with the aim of investigating the role of diverse factors involved in the etiology of bruxism. We quantified the attrition rate weekly by making superficial notches in the lower incisors and measuring the distances to the incisor edges. Repeated stimulation of the dopaminergic system with apomorphine led to an enhancement of the non-functional masticatory activity (p < 0.0001). The severity of the apomorphine-induced oral behavior was positively correlated (r(s) = 0.69, p < 0.01) with an increase in the incisal attrition rate (20.9%, p < 0.0001). Apomorphine-induced non-functional masticatory activity was strongly enhanced by the placement of an acrylic cap on both lower incisors (306%, p < 0.0001), but not by the cutting of a lower incisor. Repeated cocaine administration also increased the attrition rate (22.5%, p < 0.0001). However, neither chronic blockade of dopaminergic receptors with haloperidol, nor its withdrawal, modified attrition. In addition, since emotional disturbances are considered to be causal factors of bruxism, we tested whether experimental stress might accelerate tooth wear. Exposure to two different chronic stress regimes did not induce significant changes in incisal attrition. Moreover, exposure to chronic stress after the withdrawal of chronic haloperidol treatment did not alter attrition either. These results partially support the role of the central dopaminergic system in bruxism and suggest that stress, in general, may not be a relevant factor in tooth wear.

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.

Biochemical and functional evidence of supersensitive platelet alpha 2-adrenoceptors in major affective disorder. Effect of long-term lithium carbonate treatment.

The hypothesis that depressive illness is related to supersensitive alpha 2-adrenoceptors in the brain has been tested indirectly in blood platelets. The binding of tritiated clonidine hydrochloride to platelet membranes, a ligand that labels only the high-affinity state of the alpha 2-adrenoceptor that is coupled with cell functions, and the aggregation response induced by epinephrine hydrochloride, which is the result of the activation of the high-affinity state, were measured and correlated in 13 patients with major affective disorder. Both the number of high-affinity binding sites and the aggregation response were increased in depressed patients. There was a negative and significant correlation between both measures in the same depressed patients. Treatment with lithium carbonate (Plenur [Spain]; Linthane, comparable US product) was associated with a decrease in the high-affinity state and with an increase in the aggregation response. Thus, major effective disorder may be related to a dysfunction of the high-affinity state of the alpha 2-adrenoceptor that recognizes agonists and mediates physiological effects.