Effect of amphetamine and apomorphine on brain monoamines and behaviour in the immature and young adult rat

Abstract

In the immature rat (12-day old), amphetamine (10 mg/kg i.p.) caused an initial increase in forward locomotion, followed 15 min later by intermittent stereotyped behaviour (SB). Fifty to 65 min after injection the animals entered a phase of sleep which lasted 1-3 hrs; after this period continuous SB emerged, lasting 2-3 hrs. Brain amphetamine levels (half-life = 150 min) were elevated throughout the sequence of behavioural effects. Peak amphetamine levels were lower in the immature rat than in the adult rat. In the immature animal amphetamine caused a decrease in brain dopamine (DA) 4 hrs after injection and a sustained decrease in noradrenaline (NA) which was evident at 90 min and persisted throughout the study; a significant increase in serotonin (5HT) was evident at 15 min but had returned to normal at 90 mins. In the young adult rat (5-6 wks old), amphetamine caused an increase in forward locomotion, followed in 10-15 min by continuous SB lasting 4-4.5 hrs. The half-life of brain amphetamine was 66 min. Amphetamine increased brain DA and NA within 15 min of injection. At 90 min 5HT was elevated, DA had returned to normal but NA was still increased; thereafter the concentration of NA declined to significantly lower levels than controls and 5HT returned to normal. In the immature rat, apomorphine (10 mg/kg i.p.) caused an initial increase in locomotion which was followed 10 min later by transient intermittent SB. Following this, the animals entered a phase of sleep which lasted about 40 min before intermittent SB reemerged; this persisted for 1-2 hrs. Apomorphine caused an increase in NA and a corresponding decrease in DA at 15 and 30 mins after injection after which the levels of these amines returned to normal; 5HT levels were unchanged. In the adult rat SB commenced immediately after injection of apomorphine and lasted 70 min. There were no changes in levels of brain monoamines. There was no clear correlation between behavioural observations and levels of brain monoamines after amphetamine or apomorphine.