DIFFERENTIAL-EFFECTS OF BILATERAL DOPAMINE DEPLETION IN NEONATAL AND ADULT-RATS

Both Lesch-Nyhan syndrome and Parkinson's disease are associated with decreased brain dopamine, yet each disorder is characterized by a diff erent set of motor symptoms. Lesch-Nyhan syndrome is manifested in ear ly childhood, while parkinsonism usually does not appear until adultho od, suggesting that age at the time of dopamine loss is one determinan t of the effects of neurotransmitter deficiency. Support for this view is found in studies of animals given dopamine depleting lesions at di fferent ages and then tested in adulthood. Animals lesioned as neonate s show a supersensitivity to dopamine agonists, especially D1-dopamine receptor agonists, and to MK-801, an NMDA receptor antagonist. In add ition, neonatally treated animals show a 'priming' effect following re peated exposure to D1-dopamine agonists. Animals depleted of dopamine as adults are more supersensitive to agonists acting on the D2-dopamin e receptor, and do not evidence priming to dopamine agonists or an enh anced response to MK-801. These differential pharmacological profiles suggest that the changes in neurotransmitter systems following dopamin e depletion are, at least in parr, determined by age at the time of th e lesion. (C) 1997 Elsevier Science Ltd.