Evidence that Release of Dopamine in the Brain is Involved in the Inhibitory Effect of Cholecystokinin Octapeptide on Ingestion of Intraorally Administered Sucrose in Male Rats

Abstract

To study the possibility that release of dopamine in the brain mediates the inhibitory effect of Cholecystokinin octapeptide on ingestive behaviour, the effect of amphetamine on intake of pellets or an intraorally administered sucrose solution was compared with that of Cholecystokinin octapeptide. Additionally, comparisons were made between the effect of Cholecystokinin octapeptide and pargyline, a monoamine oxidase inhibitor, and α-methyl-ρ-tyrosine, a tyrosine hydroxylase inhibitor. While amphetamine dose-dependently inhibited pellet intake it failed to inhibit sucrose intake in doses which caused behavioural stereotypies (<800 μg). Cholecystokinin octapeptide (5 μg) inhibited ingestive behaviour in both tests. A very high dose of amphetamine (2 mg) was required to inhibit sucrose intake to a level comparable to that of Cholecystokinin octapeptide. Pargyline (5 to 25 mg) or α-methyl-p-tyrosine (25 to 100 mg) dose-dependently inhibited pellet intake but had only weak effects on the intake of sucrose. Pargyline increased the concentration of dopamine and 3-methoxytyramine in the dorsal striatum and decreased the concentration of 3,4-dihydroxyphenylacetic acid. α-Methyl-ρ-tyrosine decreased the concentration of dopamine and 3,4-dihydroxyphenylacetic acid, but not that of 3-methoxytyramine. Injection of amphetamine (2 mg), but not Cholecystokinin octapeptide, in rats pretreated with pargyline increased the concentration of 3-methoxytyramine in the dorsal striatum and this effect was blocked by pretreatment with α-methyl-ρ-tyrosine. Pretreatment with α-methyl-ρ-tyrosine partially reversed the inhibitory effect of Cholecystokinin octapeptide on sucrose ingestion, enhanced the effect of amphetamine but did not affect that of apomorphine, a dopamine agonist. The results support the possibility that the inhibitory effect of Cholecystokinin octapeptide on consummatory ingestive behaviour, in part, is mediated via release of dopamine in the brain.

Dopamine D 2 receptors and ingestive behavior: brainstem mediates inhibition of intraoral intake and accumbens mediates aversive taste behavior in male rats

“…Also, suppression of intraoral intake by apomorphine could be dissociated from the induction of behavioral stereotypies (Bednar et al 1992a). Furthermore, blockade of DA receptors or prevention of DA release in the brain attenuated the inhibitory effect of cholecystokinin octapeptide (CCK-8) on intraoral intake (Bednar et al 1992a(Bednar et al , 1992b. Because CCK-8 probably plays a physiological role in inhibition of food intake (Smith and Gibbs 1998) and, like food intake, increases the concentration of DA in the NTS (Bednar et al 1994), these results suggest that DA receptors mediate inhibition of consummatory ingestive behavior independently of their involvement in other motor functions and that this effect may be of physiological significance.…”

Norepinephrine is not required for reduction of feeding induced by cholecystokinin

“…Several reports have suggested that the effects of CCK-8 are mediated via norepinephrine (NE) (17,18,31,32,37), dopamine (2)(3)(4)(5), and/or serotonin (10,41,42,48). In the present study, we tested the hypothesis that NE is necessary for satiety induced by peripheral CCK-8.…”

Quantitation and identification of two cholecystokinin peptides, CCK‐4 and CCK‐8s, in rat brain by HPLC and fast atom bombardment mass spectrometry

“…The 1 mm thick slices were cut with a razor blade through the dorsal-ventral striatum about 1 mm anterior to the bregma. Samples from the nucleus caudatus-putamen and nucleus accumbens were punched out using stainless steel punches, 2 and 1 m m in diameter, respectively (Bednar et al, 1992). These samples were immediately placed on dry ice and stored at -70 "C until further processing.…”