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

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.