Food intake and rumen motility in dwarf goats. Effects of some serotonin receptor agonists and antagonists

Abstract

The serotonergic regulation of feeding behaviour has not so far been studied in ruminants. Therefore, the effects of some serotonin (5-HT) receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats. Goats ate less food when treated intravenously (IV) with the 5-HT precursor 5-HTP (25 micrograms, 50 micrograms or 100 micrograms kg-1 min-1 over 15 min) than when they were treated with 5-HT (which does not pass the blood-brain barrier) or with saline. Accordingly, IV dexfenfluramine infusions (50 micrograms or 100 micrograms kg-1 min-1 over 15 min), which induces release of brain 5-HT, also led to dose-related reductions in food intake. In contrast, no anorectic effects were observed after IV infusions with the selective 5-HT reuptake inhibitor fluoxetine (100 micrograms kg-1 min-1 over 15 min), the selective 5-HT1A agonist 8-OH-DPAT (0.5 micrograms kg-1 min-1 over 15 min), or eltoprazine (4 or 8 micrograms kg-1 min-1 over 15 min), a mixed 5-HT1A/5HT1B receptor agonist. None of the 5-HT antagonists tested gave any increase in food consumption in this model. Interestingly, the non-selective 5-HT receptor antagonist methysergide (360 micrograms/kg IV) reduced food intake. This effect was most noticeable at 3 h after injection. The 5-HT3 receptor antagonist ondansetron (IV 10 micrograms kg-1 min-1 over 15 min) and the peripheral 5-HT2 receptor antagonist xylamidine (IV 100 micrograms kg-1 min-1 over 10 min) failed to modify food intake. These results provide evidence for central serotonergic involvement in the control of feeding. However, this control system differs markedly in goats and rodents. Dexfenfluramine, 5-HTP and eltoprazine administered at similar dose rates to those used in the food intake experiments induced some clinical signs including inhibition of forestomach contractions. These results, together with our earlier in vivo and in vitro observations, suggest that the inhibitory effects of serotonin receptor agonists on forestomach contractions are due to interactions with both peripheral and central serotonergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, appears not to modify feeding behaviour in dwarf goats.

Food intake and rumen motility in dwarf goats. Effects of atipamezole on the inhibitory effects induced by detomidine, medetomidine and romifidine

“…Both biogenic amines are implicated in the control of food intake (Morley, 1987;Angel, 1990). In dwarf goats, 5-hydroxytryptophan (5-HTP) and dexfenfluramine, each of which enhances central serotonergic activity, produced dose-dependent reductions in food intake (Kaya et al, 1992), whereas blockade of 5-HT 1 and 5-HT 2 receptors has been shown to stimulate feeding in several species (Angel, 1990;Blundell, 1991). Central injection of adrenergic agonists has been shown to promote feeding in sheep (De Jong, 1987) and the noradrenaline-induced feeding in this species can be blocked by the a~-antagonist prazosin but not by the az-antagonist yohimbine (Miner et aL, 1990a).…”

Pharmacological and pathophysiological modulation of food intake and forestomach motility in small ruminants

“…bolus injections nor i.v. infusion with 5‐HT affected appetite in dwarf goats ( Kaya et al ., 1992 ), but inhibited forestomach contractions ( Veenendaal, 1980; Veenendaal et al ., 1980a ). Moreover, neither xylamidine ( Table 2) nor ritanserin modified feed intake as compared to control conditions ( van Miert et al ., 1989 ).…”

“…In small ruminants, the specific neurotransmitters for which there is evidence for a physiological function in feed intake regulation include the orexigenic agents noradrenaline (via α 1 ‐receptors), glutamate ( Wandji et al ., 1989 ) gamma‐aminobutyric acid (GABA)‐benzodiazepines ( de Jong, 1987; van Miert et al ., 1989 ), opioid agonist peptides ( Baile & McLaughlin, 1987; van Miert et al ., 1989 ), pancreatic polypeptides (neuropeptide‐Y; Miner et al ., 1989a,b, 1990a), and possibly melanocyte‐concentrating hormone ( Qu et al ., 1996 ); the anorectic neurotransmitters and peptides include cholecystokinin ( Della‐Fera & Baile, 1980; Baile et al ., 1983 ; Rose et al ., 1996 ), serotonin ( Blundell, 1992; Kaya et al ., 1992 ), α 2 ‐adrenoceptor agonists ( Miner et al ., 1990b ; van Miert & van Duin, 1991; van Miert et al ., 1994b ; Currie, 1996), and possibly urocortin‐corticotropin releasing factor ( Spina et al ., 1996 ), bombesin‐like peptides ( Morley, 1987; Ladenheim et al ., 1996 ) and glucagon‐like peptide 1 ( Turton et al ., 1996 ). In contrast to rodents, there is no evidence in ruminants for a central role of dopamine in feed intake regulation ( Kaya et al ., 1994 ).…”

5‐Hydroxytryptamine induces forestomach hypomotility in sheep through 5‐HT4 receptors

“…The administration of 5-HT or its precursor, 5-hydroxytryptophan (5-HTP), inhibits the reticulorumen primary cycles in goats (Veenendaal et al 1980;Kaya, van Duin, Veenendaal Ruckebusch & Ooms, 1983;Sorraing et al 1984Sorraing et al , 1985 and also depresses rumcn secondary contractions (Sorraing et al 1984) and omasum activity (Plaza et al 1994b). Concomitantly, 5-HT induces an antroduodenal phase III-like pattern of the MMC (Ruckebusch, 1984;Ruckebusch & Bardon, 1984), as well as a release of somatostatin and bombesin, peptides which are also involved in the origin of the MMC (Plaza, Arruebo & Murillo, 1996a,b).…”

“…Taken together, these findings suggest that 5-HT4 receptors are involved in the effects of intravenous 5-HT on gastrointestinal motility in sheep. Nevertheless, 5-HT1, 5-HT2 and 5-HT3 agonists also inhibit reticulorumen primary cycles in sheep (Brikas et al 1994;Plaza et al 1994b) and goats (Kaya et al 1992), and delay rumen secondary contractions and inhibit omasum motility in sheep (Plaza et al 1994b). Moreover, they evoke a phase III-like pattern (Plaza et al 1992(Plaza et al , 1994, suggesting that these receptors may also be involved in the effects of 5-HT.…”