Antiaversive properties of opioids in the conditioned taste aversion test in the rat.

The antiaversive effect of mu-, kappa- and delta-opioid receptor agonists against conditioned taste aversion (CTA) induced by apomorphine, lithium chloride and copper sulphate in the rat was studied, in order to evaluate whether prevention of CTA is a suitable model for the study of antiemetics. Anti-aversion was not a general characteristic of all opioid substances tested. Only one dose of the mu-agonist morphine and only one dose of the kappa-agonist ethylketocyclazocine had a consistent antiaversive effect against CTA induced by apomorphine; one dose of the delta-agonist [D-Ala2, Met5]enkephalinamide antagonized the aversion induced by lithium chloride. As the results do not correspond to our previous findings on the antiemetic effects of these opioids in the dog (all mu- and kappa-agonists tested having an antiemetic effect), we conclude that the CTA test cannot be used as a screening test for potentially antiemetic drugs.

Influence of isaxonine on reinnervation of the rat gastrocnemius muscle.

Isaxonine is reported to have a favourable effect on nerve regeneration. The histological and histochemical changes were compared in the gastrocnemius muscles of 20 rats, in which the left sciatic nerve was frozen-crushed for 10 s at the level of the buttock. The animals received a daily dose of intraperitoneal isaxonine and ten others the solvent only. After 8 weeks small type grouping was seen in rats receiving solvent only and large type grouping in rats treated with isaxonine. After 10 weeks a checkerboard pattern of the fibre types was observed in the muscles of animals receiving solvent only but fibre type grouping was present in those treated with isaxonine. This experiment indicates that isaxonine prevents synaptic remodelling by suppression of the redundant nerve endings from additional axons, which have regenerated more slowly, in making contact with motor endplates.

Emetic and antiemetic effects of opioids in the dog.

The emetic and antiemetic effects of opioid agonists were studied in awake dogs. The mu-agonists morphine, fentanyl and methadone, in sedative doses, prevented the emetic response to apomorphine and copper sulphate; only morphine induced emesis, at doses lower than those required to prevent emesis. The delta-agonist [D-Ala2,Met5]enkephalinamide (DALA) and [Leu5]enkephalin induced emesis in some of the dogs studied but had no antiemetic activity. The kappa-agonists bremazocine and ethylketocyclazocine (EKC) did not induce emesis but, at sedative doses, prevented the emetic response to apomorphine. The emetic effect of DALA was antagonized by naloxone in some dogs; the antiemetic effect of morphine, bremazocine and EKC was blocked by both naloxone and MR 2266. The non-opioid sedatives diazepam, phenobarbital and xylazine, administered in sedative doses, did not prevent apomorphine-induced emesis. Our results suggest that a delta-receptor is involved in the emetic effect and a mu- and/or or kappa-receptor in the antiemetic effect of opioids.

Influence of isaxonine on the target phenomenon, muscle fibre size and neuromuscular junction in the tenotomized and denervated gastrocnemius muscle of the rat.

Isaxonine is reported to accelerate the rate of peripheral nerve regeneration, stimulate axonal sprouting and promote motor and sensory function recovery. The target phenomenon in muscle fibers is the morphological expression of increased stretch activity in a diseased muscle. It can be produced in the gastrocnemius muscle of the rat by tenotomy and is inhibited by simultaneous denervation. The influence of isaxonine on this experimental model was studied. Twenty Wistar rats were submitted to bilateral section of the Achilles tendon and section of the left sciatic nerve. In ten rats, treated with isaxonine, the qualitative and quantitative changes in the gastrocnemius muscle were compared with the control group over a period of 3 weeks. No statistical differences were observed in the occurrence and inhibition of the target phenomenon, the muscle fibre size and the neuromuscular junction. Isaxonine has no direct effect on a diseased muscle with an intact nerve supply, nor in the early stages after complete denervation.

Influence of peripheral and central administration of apomorphine and morphine on intragastric pressure in the dog.

Apomorphine was about 30 times more potent in inducing gastric relaxation when applied intracerebroventricularly (i.c.v.) than when injected intravenously (i.v.) in the conscious dog. In the anesthetized dog, the dose of apomorphine producing gastric relaxation via the vertebral artery was at least 10 times lower than that needed to produce gastric relaxation via the i.v. route. For morphine, similar doses had to be given i.c.v. and i.v. to obtain the same degree of gastric relaxation in the conscious dog; in the anesthetized dog, morphine was 3 times more potent via the vertebral artery than i.v. The results suggest that apomorphine-induced gastric relaxation in the dog is mediated via a central site located in the region supplied by the vertebral artery, but that the gastric relaxatory effect of morphine is mediated by both a peripheral and a central site of action.