Differential nicotinic receptor expression in monkey basal ganglia: Effects of nigrostriatal damage
Section snippets
Animal treatment
Twenty squirrel monkeys (Saimiri sciureus) of either sex weighing between 0.595 and 0.752 kg were obtained from Osage Research Primates (Osage Beach, MO, USA). Animals had free access to food and water and were exposed to a 13/11-h light/dark cycle. All procedures used in this study conform to the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee.
Prior to treatment, locomotor activity was assessed using a computerized
MPTP treatment
Monkeys were treated with MPTP as described in Experimental procedures to selectively damage the dopaminergic nigrostriatal system. The animals were divided into two groups, one with moderate and the other with a more severe nigrostriatal damage, using declines in the striatal dopamine transporter as an index of dopaminergic loss (Alexander et al., 1992, Rioux et al., 1997, Schneider et al., 1999). Overall, 125I-RTI-121 binding was reduced to 28% and 23% in the caudate and putamen,
Discussion
Extensive evidence indicates that the basal ganglia are anatomically heterogeneous and composed of distinct nigral neuronal populations that project to divergent striatal areas (Parent et al., 1983, Schneider et al., 1987, Gibb et al., 1990, Fearnley and Lees, 1991, Haber et al., 2000). In addition, it has been shown that various neurotransmitter receptors, transporters and enzymes are organized in distinct ventromedial to dorsolateral gradients in the striatum (Kemel et al., 1989, Desban et
Conclusions
Our data show that in the striatum alterations in α-CtxMII sensitive nicotinic receptors parallel those in the dopamine transporter, while in the substantia nigra changes in both α-CtxMII sensitive and insensitive sites are linked to the transporter, a dopaminergic neuronal marker. Furthermore, our competition studies show that the majority of striatal 125I-α-CtxMII sensitive sites are lost after MPTP treatment, whereas both 125I-α-CtxMII and 125I-epibatidine sites are similarly reduced in the
Acknowledgements
This work was supported by the California Tobacco Related Disease Research Program, #7RT-0015 and #8RT-0105.
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