Long-term methamphetamine-induced decreases of [11C]WIN 35,428 binding in striatum are reduced by GDNF: PET studies in the vervet monkey
✍ Scribed by William P. Melega; Goran Laćan; Antonio A.F. Desalles; Michael E. Phelps
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 102 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
The effects of glial cell line-derived neurotrophic factor (GDNF) pretreatment on methamphetamine (METH)-induced striatal dopamine system deficits in the vervet monkey were characterized with [ 11 C]WIN 35,428 (WIN)-positron emission tomography (PET). WIN, a cocaine analog that binds to the dopamine transporter (DAT), was used to provide an index of striatal dopamine terminal integrity. In two subjects, GDNF (200 µg/40 µl) was injected into the caudate and putamen unilaterally vs. saline contralaterally. After 1-2 weeks, ϩ and -GDNF striatal WIN-PET binding values were equivalent as calculated by multiple time graphic analysis, suggestive of an absence of unilateral DAT up-regulation. Three other subjects (n ϭ 3) received GDNF injections into the caudate and putamen unilaterally and one week later, were administered METH HCl (2 ϫ 2 mg/kg; i.m., 24 hours apart; a neurotoxic dosage for this species). At 1 week post-METH, WIN-PET studies showed that mean WIN binding was decreased by 72% in the ϩGDNF and by 92% in the -GDNF striatum relative to pre-drug assessment values. Thus, GDNF pretreatment reduced the extent of METH-induced decreases in WIN binding. Subsequent WIN-PET studies (1.5-9-month range) showed a protracted recovery of WIN binding in each striatum, indicative of long-term but partially reversible METH neurotoxicity. Further, at each time point, WIN binding remained relatively higher in the ϩGDNF vs. -GDNF striatum. These results provide further evidence that the adult non-human primate brain remains responsive to exogenously administered GDNF and that this pharmacotherapy approach can counteract aspects of neurotoxic actions associated with methamphetamine.