Hyperactivity in neonatally dopamine-lesioned rats requires residual activity in mesolimbic dopamine neurons.
Neonatal destruction of mesencephalic dopamine (DA) neurons in rats through administration of 6-hydroxydopamine (6-OHDA; 75 micrograms IC) leads to locomotor hyperactivity at adulthood. Treatment with the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (H44/68; 250 mg/kg) was shown to reduce the motor activity of neonatally 6-OHDA-lesioned rats to activity levels similar to controls. In both animal groups, DA and metabolite tissue levels decreased after the H44/68 treatment. However, the extent of the H44/68-induced DA decrease was less pronounced in the 6-OHDA-lesioned animals, with no change at all in the dorsal striatum. These results imply that residual activity in mesolimbic DA neurons is required for maintaining the hyperactivity seen after neonatal 6-OHDA lesions, and that this hyperactivity is apparently mediated by postsynaptic alterations.
Luthman
J
J
Preclinical R&D, Astra Arcus AB, Södertälje, Sweden.
Lindqvist
E
E
Ogren
S O
SO
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015306:Biogenic Monoamines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D015306:Biogenic Monoamines; D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine