Is there a significant somatodendritic uptake of dopamine in the substantia nigra? Evidence from the weaver mutant mouse.
Slices of the substantia nigra from normal mice and from mice with the weaver gene were used to study somatodendritic uptake of dopamine. The substantia nigra of the homozygous weaver mouse is deficient in both cell bodies and dendrites whereas the substantia nigra of the heterozygous weaver mouse is deficient only in dendrites. Accumulation of [3H]dopamine by nigral slices obtained from each genotype was not different from that observed in slices obtained from control mice. The observed accumulation of [3H]dopamine was apparently taking place predominantly into serotonergic and noradrenergic elements since significant reductions were obtained by both fluoxetine and desipramine at concentrations that were selective for the serotonin and norepinephrine carriers, respectively. In the absence, as well as in the presence of fluoxetine and desipramine, dopamine accumulation in the substantia nigra was only slightly attenuated by the known dopamine uptake blocker GBR 12909. These data argue against a significant presence of somatodendritic uptake systems for dopamine in the substantia nigra and suggest that caution be used in the interpretation of results from studies on dopamine release from nigral slices when [3H]dopamine has been used to preload the tissue. Under such experimental conditions, it is likely that a large proportion of the released tritium might come from neurons other than those which contain endogenous neurotransmitter dopamine.
Simon
J R
JR
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202-4887.
Ghetti
B
B
D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D051379:Mice; D008818:Mice, Neurologic Mutants; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D005473:Fluoxetine; D012701:Serotonin; C043425:vanoxerine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine