mise à jour du
21 mars 2010
Pharmacol Biochem Behav
LHRH antagonizes yawning and genital grooming
induced by apomorphine in rats
Mora S and Diaz-Veliz G
Departamento Preclinicas, Facultad de Medicina, Universidad de Chile, Santiago


The effects of the pretreatment with LHRH on the behavioral effects induced by low doses of apomorphine were studied in male rats. Three doses of apomorphine (31.25, 62.50 and 125 µg/kg) were subcutaneously administered two hours after LHRH 100 µg/kg or solvent SC treatment. Apomorphine induced repeated episodes of yawning and genital grooming. Pretreatment with LHRH abolished or reduced yawning and genital grooming induced by the three doses of apomorphine, suggesting that the peptide could induce subsensitivity of DA receptors responsible for yawning and genital grooming.
Recent reports have postulated that LHRH is capable of modulating dopamine (DA) transmission in experimental animals. In fact, behavioral and biochemical findings support the hypothesis of an inhibitory effect of LHRH upon presynaptic synthesis and release of DA. Incubation of rat corpus striatum synaptosomes in the presence of LHRH decreased DA synthesis. Subcutaneous and intracerebral injection of LHRH in rats inhibited a conditioned avoidance response, which is considered as a characteristic of drugs which block DA transmission. In addition, LHRH is able to antagonize the stimulatory effect induced by amphetamine on motor activity and acquisition of conditioned avoidance responses. L-DOPA, precursor of DA, reverted the inhibitory effects of LHRH and counteracted the antagonistic effect of LHRH on the action of amphetamine.
The administration of small doses of apomorphine produces a behavioral syndrome characterized by hypomotility, yawning, penile erection and genital grooming. These effects are considered to be the consequence of the stimulation of presynaptic DA receptors in the CNS. The purpose of the present study was to provide further evidence for a possible interaction between LHRH and DA mechanisms. We studied the influence of LHRH on the behavioral effects induced by low doses of apomorphine. The results indicate that pretreatment with LHRH antagonized yawning and genital grooming induced by apomorphine in rats.
The present findings indicate that exogenously administered LHRH antagonizes the behavioral effects of low doses of apomorphine, namely yawning and genital grooming. These effects, which include hypomotility, are considered to be due to an activation of DA receptors in the CNS. There is evidence suggesting that DA receptors mediating yawning might be identified with presynaptic DA autoreceptors. However, recent reports postulate that DA receptors mediating yawning are a special population of postsynaptic DA receptors of the D2 type with a high affinity for DA and apomorphine. Although apomorphine is a mixed D1-D2 agonist its potency for Dl receptors is only in the micromolar range. Then the small doses of apomorphine that were used in this study are likely to stimulate selectively D2 receptors.
Yawning has been proposed to be a reliable behavioral sign of DA agonistic action of drugs. Furthermore, it has been suggested that yawning could be useful in the screening of drugs. 1f in a screening observation a given substance induces yawning in rats, which is blocked by DA antagonists, there is a high probability that the compound possesses DA receptor agonistic properties. Consequently, if a given drug abolishes apomorphine-induced yawning it could be classified as a DA antagonist. In fact, neuroleptics reduce yawning induced by apomorphine and other putative DA receptor agonists but do not abolish the yawning induced by cholinergic drugs.
Yawning behavior and genital grooming are also induced by protein hormones from the pituitary, such as ACTH, alpha-MSH and oxytocin. They have been postulated as mediators in the behavioral effects of low doses of apomorphine. Recently it has been reported that low doses of prolactin injected systemically induce yawning in male rats, maybe through the release of small amounts of DA from the striatum. On the other hand, hypophysectomy inhibits yawning, penile erection and genital grooming but not the hypomotility induced by small doses of apomorphine, suggesting that the lack of some pituitary hormones alters the sensitivity of DA receptors responsible for these effects, but not those responsible for the reduction of motor activity. Gonadal steroids seem to exert opposite effects on apomorphine-induced yawning in male rats. Whereas testosterone facilitates both yawning and penile erection, castration and exogenously administered estrogens antagonize them. Besides, apomorphine is less effective in inducing yawning in female than in male rats. According to Serra et al., subsensitivity of DA receptors may explain the reduction of this behavioral response observed in males following estrogen treatment or in normal female animals.
The present results show that the hypothalamic hormone LHRH, as well as hypophysectomy and castration, prevents yawning and genital grooming induced by apomorphine. We can speculate that LHRH is also able to influence the effect of apomorphine by inducing subsensitivity of DA receptors which mediate these behaviors. The possibility that LHRH modulates DA activity was suggested in recent reports. The peptide antagonizes the motor hyperactivity, rearing behavior and the increase in the conditioned responses induced by amphetamine and this antagonism is reverted by L-DOPA, the precursor of DA synthesis. Besides, there is biochemical evidence of an inhibitory effect of LHRI-I upon DA synthesis. Thus, the decrease in DA transmission should exert inhibitory effects on apomorphine-induced yawning. In fact, acute depletion of brain DA by short-term reserpine or alpha-methyltyrosine pretreatment reduces the ability of D2 agonists to induce yawning. Longoni et al. have postulated that D2 receptors mediating yawning appear to be functionally linked to Dl receptors in such a way that endogenous DA by stimulating Dl receptors plays a permissive role for the expression of yawning induced by postsynaptic D2 agonists.
Finally, the observation that LHRH does not appear to block the hypomotility produced by low doses of apomorphine (16) suggests that hypomotility and yawning could be mediated through the activation of different kinds of high affinity D2 receptors, which are probably located pre- and post synaptically, respectively.