The participation of central cholecystokinin-8 (CCK-8) receptors in the modulatory effect of D-Ala2, N-Me-Phe4, Gly5-ol enkephalin (DAGO), a selective mu-opioid receptor agonist, on the spike burst activity of the gastrointestinal tract (rumen, reticulum, antrum, duodenum, colon and caecum) in sheep was investigated. DAGO was infused intracerebroventricularly (i.c.v.) at doses of 0.1-1 microg/kg body weight (BW). It was shown that DAGO significantly inhibited myoelectrical activity of the wall of the forestomachs, abomasum and colon but stimulated this activity in the duodenum (rate of myoelectrical migrant complex-MMC). The effects of DAGO were prevented by CCK-8 antagonists (L-364.718 and L-365.260) previously infused at doses of 5-20 microg/kg BW. The results of this present study indicate that central receptors of CCK-8 participated in the modulatory action of an opioid on myoelectrical activity of the gastrointestinal tract in sheep. Furthermore, this result suggests that CCK-8 is released in response to mu-receptor stimulation, because CCK-8 antagonists (L-364.718 and L-365.260) prevented the modulatory action of DAGO on the gastrointestinal motility in sheep.

The effect of various degrees of 5 min duodenum distention (performed with a balloon filled with 20, 30, 40 or 80 ml of water, DD 20-DD 80) on spike bursts and motility of the forestomach and abomasum was investigated in sheep which, under general anaesthesia, had electrodes inserted into the muscular layers of the forestomachs, abomasum and duodenum, as well as into fistulas in the muscular layers of the rumen.Duodenal distention of DD 20 to DD 30 ml did not change the frequency of spike bursts or reticulo-ruminal motility, but significantly increased the amplitude of contractions (F=74.40 and F=l 10.02; PO.001, respectively). In some animals a change in behaviour was observed (the animals shifted their weight from one foot to the other, urinated and/or defecated, looked around). Five min duodenal distention of DD 40 and DD 80 caused immediate and complete inhibition lasting for about 10 min of both the frequency of spike bursts and reticulo-ruminal contractions (F=43.46; PO.001 and F=44.37; PO.001, respectively) as well as of the amplitude of contractions (F= 142.25 and F=236.48; PO.001, respectively). All animals showed the following signs: stretching their bodies, bleating, gnashing of teeth, lying down, urinating and defecating. Blood plasma Cortisol level increased significantly during gastrointestinal motility inhibition from 16.23±1.12 to 42.7±7.2 (F=58.88; PO.001) during DD 40 and from 19.58±1.81 to 56.6 ±5.7 ngml" 1 30 min after the end of DD 80 ml (F=25.47; PO.001).Duodenal distention inhibited forestomach motility proportionately to the degree of distention (F=31.87; PO.001). This reaction is called the viscero-visceral inhibitory reflex. Moreover, it caused * Supported by State Committee for Scientific Research, Grant No 5PO6K0301 234 DUODENAL DISTENSION STRESS IN SHEEP a change in animal behaviour and a significant increase in the plasma Cortisol concentration, testifying to the fact that this is a general reaction to pain as a stressor.The obtained results show that the model is sufficient to cause stress. It also allows the gradation of stress intensity. It can be concluded, therefore, that the above model can be used in testing anticolic drugs.