Increased self-administration of d-amphetamine by rats pretreated with metergoline.

Rats trained to self-administer d-amphetamine were pretreated with metergoline, a long-acting 5-hydroxytryptaminergic antagonist, and immediately placed in self-administration cages for 8 hours. During the first 3 hours after metergoline the normal pattern of d-amphetamine self-administration was unaltered, but thereafter the rate of self-injections was increased. Between 4 and 6 hr the self-injections in metergoline-treated rats were increased in a regular fashion and subsequently (7-8 hr) in a stereotyped manner, i.e., rapid bursts of lever presses with little space between injections. In amphetamine-naive rats the levels of striatal and nucleus accumbens dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, rose with time after metergoline injection. Levels of 5-hydroxyindoleacetic acid remained unchanged in these brain areas. The neurochemical results suggest a correlation between the dopaminergic actions of metergoline and d-amphetamine self-administration.