A direct comparison of amphetamine-induced behaviours and regional brain dopamine release in the rat using intracerebral dialysis.
Sharp T., Zetterström T., Ljungberg T., Ungerstedt U.
An intracerebral microdialysis method was used in awake rats to directly compare the effect of amphetamine on dopamine (DA) release in the striatum and nucleus (n.) accumbens with alterations in behaviour. Amphetamine (0.5-5.0 mg/kg, s.c.) caused a dose-dependent release of DA in both brain regions; however the n. accumbens appeared for the most part more sensitive to amphetamine than the striatum. At each individual dose of the drug, 0.5, 2.0 and 5.0 mg/kg s.c., DA release was closely followed over the time course by the overall behavioural syndrome. Certain components of behaviour showed a regional-specific association with DA release. The intensity of stereotyped head and forepaw movements was closely correlated over the dose range with the amount of DA released in striatum but not n. accumbens. Over the time course, however, the occurrence of this behaviour was delayed compared to increased striatal DA release. In contrast, increased locomotor activity was correlated with the time course change in, and amount of, DA released in n. accumbens by low doses of amphetamine, but not at any dose with DA released in striatum. Repetitive sniffing was better correlated with DA released in n. accumbens than striatum. These in vivo measurements of DA release add further support to the hypothesis that amphetamine-induced stereotypy and locomotion are mediated via DA released in striatum and n. accumbens, respectively. Our data suggest that the occurrence of intense stereotypy rather than locomotor activity at high doses of amphetamine is not due to a selection action in striatum but probably competition between the two behaviours.(ABSTRACT TRUNCATED AT 250 WORDS)