The purpose of the present investigation was to test the hypothesis that drug-induced changes in rumen contractions influence feed intake in dwarf goats. Intravenous (i.v.) administration of clonidine (1 microgram kg-1 min-1 for 10 min), xylazine (1 microgram kg-1 min-1 for 10 min), and PGF-2 alpha (10 micrograms kg-1 min-1 for 15 min) caused bradycardia and inhibition of rumen contractions. However, no appetite-stimulating effect of these drugs was observed. Other clinical changes induced by the alpha-adrenergic agonists included slight sedation and a decrease in body temperature; all clinical effects of clonidine and xylazine were partly antagonized by tolazoline pretreatment (10 micrograms kg-1 min-1 for 30 min). These results suggest that the CNS control of feeding differs in ruminants and monogastric species. In dwarf goats fasted for 2 h, i.v. administration of oxytocin (0.01 IU kg-1 min-1 for 15 min), vasopressin (0.01 IU kg-1 min-1 for 15 min), octapressin (0.003 IU kg-1 min-1 for 15 min) or PGE1 (0.8 microgram kg-1 min-1 for 15 min) did not change feeding behaviour during the two observation periods (0-30 min and 180-210 min after drug infusion, respectively). In previous studies, similar doses of these drugs induced changes in heart rate and inhibition of rumen contraction in goats. These findings demonstrate that drug-induced changes in forestomach contractions do not simply cause changes in feeding behaviour. The i.v. infusion of the PGF 2 alpha analogues etiproston (10 micrograms kg-1 min-1 for 15 min), luprostiol (30 micrograms kg-1 min-1 for 15 min), cloprostenol (1 microgram kg-1 min-1 for 15 min) and tiaprost (1 microgram kg-1 min-1 for 15 min) induced hypophagic effects and stimulated intestinal propulsion.

No abstract

Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick-borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (n = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration-time curves for both drugs followed first-order two-compartment decay. For TMP, mean t1/2 beta +/- SEM (h) was 0.84 +/- 0.06 (i.v. control) and 0.90 +/- 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 +/- 0.31 (i.v. control) and 10.28 +/- 0.67 (i.v. infected) were obtained (P less than 0.05). Mean Vd beta +/- SEM values (l/kg) were 3.84 +/- 0.27 (i.v. control) and 4.07 +/- 0.85 (i.v. infected) for TMP (NS) and 7.02 +/- 0.63 vs 9.29 +/- 0.21 (P less than 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P less than 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 +/- 0.06 micrograms/ml and 0.85 +/- 0.17 microgram/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 +/- 0.01 microgram/ml and the maximum was reached after 1.2 +/- 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 +/- 0.02 microgram/ml with Tmax of 22.5 +/- 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.

The effects of some alpha 2-adrenoceptor agonists and of the alpha 2-adrenoceptor antagonist atipamezole on food intake and ruminal contractions were studied in dwarf goats. Detomidine, 0.2 microgram/kg per min for 10 min, failed to modify food intake during either the first or second observation period (0-30 min and 180-210 min after drug infusion, respectively). Given at a higher dose rate (0.4 microgram/kg per min for 10 min), the drug inhibited food consumption during the first observation period, but stimulated food intake during the second period. A similar pattern was observed after IV infusion with medetomidine (0.2 microgram/kg per min for 10 min), romifidine (0.4 microgram/kg per min for 10 min) or xylazine (1 microgram/kg per min for 10 min). The alpha 2-antagonist atipamezole (2 micrograms/kg per min for 10 min) failed to modify food intake during either the first or second observation period. After treatment with atipamezole, the effects of alpha 2-agonists on feeding behaviour were completely antagonized. The alpha 2-agonists administered at similar dose rates to those used in the food intake experiments induced bradycardia, decreases in body temperature and inhibition of ruminal contractions. The inhibition of ruminal contractions induced by romifidine was partly antagonized by atipamezole pre-treatment. These findings demonstrate that the alpha 2-agonist-induced changes in ruminal contractions do not simply cause changes in feeding behaviour. The drop in body temperature induced by alpha 2-agonists was prevented by atipamezole pre-treatment, whereas the induced bradycardia was not modified by this alpha 2-antagonist.

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.