Appetite-modulating drugs in dwarf goats, with special emphasis on benzodiazepine-induced hyperphagia and its antagonism by flumazenil and RO 15-3505.
In dwarf goats fasted for 2 h, i.v. administration of the benzodiazepine (BZ) agonists diazepam (60 micrograms/kg), brotizolam (2 and 4 micrograms/kg) and climazolam (100 micrograms/kg) induced hyperphagic effects, whereas i.v. injections of the BZ-antagonist flumazenil (R degrees 15-1788; 0.5 mg/kg), the anthelmintic ivermectin (0.1 mg/kg), the 5-HT2 antagonist ritanserine (0.1 mg/kg), ACTH (10 micrograms/kg) and prednisolone (1 mg/kg) were inactive in a 30-min feeding test. Both the BZ-antagonist R degrees 15-3505 (greater than or equal to 0.1 mg/kg) and the opiate receptor antagonist naloxone (0.1 mg/kg) had anorectic effects in dwarf goats given 30 min access to a palatable pelleted concentrate. The hyperphagic effects of climazolam and brotizolam were not antagonized by flumazenil, whereas similar doses of this drug completely reversed muscle incoordination and ataxia induced by much higher doses of these BZ-agonists. In the combination experiments with naloxone and BZ-agonists, naloxone antagonized the hyperphagic effects of both diazepam and brotizolam. Similarly, in the diazepam-R degrees 15-3505 study, there was a significant effect of diazepam and a significant inhibition of this effect by R degrees 15-3505 (50 micrograms/kg). In the diazepam-ivermectin combination experiment no evidence for drug potentiation was found. These results and the mode of action of the above mentioned drugs are discussed in relation to feeding behaviour.
Van Miert
A S
AS
Department of Veterinary Basic Sciences, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
Koot
M
M
Van Duin
C T
CT
D000818:Animals; D014151:Anti-Anxiety Agents; D001069:Appetite Regulation / Q000187:drug effects*; D001381:Azepines / Q000494:pharmacology; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D001835:Body Weight; D003975:Diazepam / Q000494:pharmacology; D005260:Female; D005442:Flumazenil / Q000494:pharmacology*; D006041:Goats / Q000502:physiology*; D006963:Hyperphagia; D007559:Ivermectin / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D014151:Anti-Anxiety Agents; D001381:Azepines; D001570:Benzodiazepinones; D001569:Benzodiazepines; D005442:Flumazenil; C020960:brotizolam; D007559:Ivermectin; C040725:Ro 15-3505; C035147:climazolam; D003975:Diazepam; D008874:Midazolam