PMID- 16890350 OWN - NLM STAT- MEDLINE DCOM- 20061103 LR - 20131121 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 406 IP - 1-2 DP - 2006 Oct 2 TI - CGP 56999A, a GABA(B) receptor antagonist, enhances expression of brain-derived neurotrophic factor and attenuates dopamine depletion in the rat corpus striatum following a 6-hydroxydopamine lesion of the nigrostriatal pathway. PG - 102-6 AB - Rats were injected (i.p.) once daily with either 1 mg/kg CGP 56999A, a gamma-aminobutyric acid(B) (GABA(B)) receptor antagonist, or an equivalent volume of saline beginning 7 days prior to, and continuing for 7 days following, a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine (DA) pathway. At the end of the CGP 56999A treatment period the concentrations of DA and dihydroxyphenylacetic acid (DOPAC), as well as the expression of brain-derived neurotrophic factor (BDNF), were analyzed in corpus striatum ipsilateral and contralateral to the lesioning. No significant differences in these parameters were noted in the contralateral striatum between saline- and CGP 56999A-treated subjects. In contrast, as compared to animals receiving saline only, daily treatment with the GABA(B) receptor antagonist significantly attenuated the 6-hydroxydopamine-induced decline in DA and increased the expression of BDNF in the ipsilateral striatum. The results indicate that CGP 56999A enhances BDNF gene expression in the rat corpus striatum and prevents the decline in DA content that is a characteristic sequela of 6-hydroxydopapmine lesions of the nigrostraital dopamine pathway. These findings suggest that GABA(B) receptor antagonists may be of value in the treatment of Parkinson's disease and other conditions that would benefit from an enhanced production of neurotrophic factors in brain. FAU - Enna, S J AU - Enna SJ AD - Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA. FAU - Reisman, Scott A AU - Reisman SA FAU - Stanford, John A AU - Stanford JA LA - eng GR - AG023549/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060804 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (CGP 56999A) RN - 0 (GABA Antagonists) RN - 0 (GABA-B Receptor Antagonists) RN - 0 (Phosphinic Acids) RN - 0 (Receptors, GABA-B) RN - 0 (Sympatholytics) RN - 102-32-9 (3,4-Dihydroxyphenylacetic Acid) RN - 8HW4YBZ748 (Oxidopamine) RN - VTD58H1Z2X (Dopamine) SB - IM MH - 3,4-Dihydroxyphenylacetic Acid/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/*drug effects/metabolism MH - Corpus Striatum/*drug effects/metabolism/physiopathology MH - Denervation MH - Disease Models, Animal MH - Dopamine/*metabolism MH - GABA Antagonists/*therapeutic use MH - GABA-B Receptor Antagonists MH - Gene Expression/drug effects/physiology MH - Male MH - Neural Inhibition/drug effects/physiology MH - Neural Pathways/metabolism/physiopathology MH - Oxidopamine MH - Parkinsonian Disorders/*drug therapy/metabolism/physiopathology MH - Phosphinic Acids/*therapeutic use MH - Rats MH - Rats, Inbred F344 MH - Receptors, GABA-B/metabolism MH - Substantia Nigra/metabolism/physiopathology MH - Sympatholytics MH - Synaptic Transmission/drug effects/physiology MH - Treatment Outcome MH - Up-Regulation/drug effects/physiology EDAT- 2006/08/08 09:00 MHDA- 2006/11/04 09:00 CRDT- 2006/08/08 09:00 PHST- 2006/01/09 00:00 [received] PHST- 2006/05/19 00:00 [revised] PHST- 2006/07/10 00:00 [accepted] PHST- 2006/08/08 09:00 [pubmed] PHST- 2006/11/04 09:00 [medline] PHST- 2006/08/08 09:00 [entrez] AID - S0304-3940(06)00713-0 [pii] AID - 10.1016/j.neulet.2006.07.004 [doi] PST - ppublish SO - Neurosci Lett. 2006 Oct 2;406(1-2):102-6. doi: 10.1016/j.neulet.2006.07.004. Epub 2006 Aug 4.