mise à jour du
6 novembre 2005
Behav Neural Biol.
Opiate influences on drug-induced yawning in the rat
Berendsen HHG , Gower AJ
Department of CNS Pharmacology, Organon, Oss, The Netherlands


Yawning can be elicited in laboratory animals by various pharmacological agents including apomorphine and physostigmine (Yamada and Furukawa, 1980; Holmgren et al, 1980). The response has been shown to be influenced by androgens: castration will reduce drug-induced yawning and pretreatment with testosterone will restore it (Berendsen and Nickolson, 1980; Holmgren et al, 1980). Since several studies, e.g. Cicero et al. (1980), indicate an interaction between androgens and opiates, we tested whether an opiate link was involved in the effect of testosterone on yawning.
All experiments were carried out between 8.30-12.30, using naive male Wistar rats weighing 250-350 g. The effects of naloxone HCl, morphine HCl, haloperidol and atropine SO4, injected subcutaneously (s.c.) 20 min. before testing, were determined on apomorphine HCl (40 and 80 µg/kg s.c.) or physostigmine salicylate (100 pg/kg s.c.) induced yawning in normal animals. Yawning responses were observed in perspex observation cages (7.5 x 18 x 30 cm) as described previously (Berendsen and Nickolson, 1980) over a 20 min. period starting immediately after apomorphine or 10 min. after physostigmine. The effects of single doses of naloxone, morphine, haloperidol and atropine were also determined on the dihydrotestosterone propionate-(DHTP) mediated increases in apomorphine-induced yawning in chronically castrated (at least 6 weeks) rats. DHTP, 125 µg/rat/day or arachis oil was injected s.c. once daily for 3 consecutive days. 24 h. later test drugs were injected s.c. 20 min. prior to apomorphine (80 µg/kg) and yawning scored as stated above.
Naloxone (1-10 mg/kg) partially antagonised apomorphine or physostigmine-induced yawning. In castrated rats, naloxone, 10 mg/kg inhibited the DHTP mediated increases but had no effect on the low level residual apomorphine yawning. In normal rats, 0.32 and 1 mg/kg morphine had no effect on apomorphine yawning but 3.2 mg/kg caused marked inhibition; morphine (0.32-3.2 mg/kg) produced dose related inhibition of physostigmine yawning. In castrated rats, morphine, 1 mg/kg, inhibited the residual apomorphine response but had no significant effect on the DHTP-mediated increases. Haloperidol (0.01-0.1 mg/kg) reduced apomorphine yawning in normal rats. Haloperidol 0.01 mg/kg significantly increased physostigmine yawning but higher doses, 0.03 and 0.1 mg/kg had no significant effect. Atropine reduced both apomorphine and physostigmine yawning. In castrated rats, haloperidol 0.1 mg/kg and atropine 10 mg/kg inhibited both residual apomorphine yawning and the DHTP-mediated increases.
The finding that naloxone could not completely block yawning in normal rats, but blocked the DHTP effects suggests that this drug inhibits drug-induced yawning by antagonising the androgenic influences. However, in these experiments, there was no evidence that morphine treatment will enhance yawning. The blocking by haloperidol and atropine of yawning in normal rats and in castrated rats treated with DHTP or arachis oil, supports the hypothesis that DHTP acts as a permissive agent on yawning (Berendsen and Nickolson, 1980). The effects of these drugs also confirm previous findings (Yamada and Furukawa, 1980) of an interaction between dopaminergic and cholinergic effects on yawning.
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