Buprenorphine modulates methamphetamine-induced dopamine dynamics in the rat caudate nucleus.
Methamphetamine (METH) abuse and addiction present a major problem in the United States and globally. Oxidative stress associated with exposure to METH mediates to the large extent METH-evoked neurotoxicity. While there are currently no medications approved for treating METH addiction, its pharmacology provides opportunities for potential pharmacotherapeutic adjuncts to behavioral therapy in the treatment of METH addiction. Opioid receptor agonists can modulate the activity of dopamine neurons and could, therefore, modify the pharmacodynamic effects of METH in the dopaminergic system. Efficacy of the adjunctive medication with buprenorphine has been demonstrated in the treatment of cocaine addiction extending beyond opiate addiction. We investigated the interactions of morphine (10 mg/kg) and buprenorphine (0.01 and 10 mg/kg) with METH (2 mg/kg) affecting striatal dopaminergic transmission. The extracellular concentration of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were determined using brain microdialysis coupled with high performance liquid chromatography with electrochemical detection (HPLC-ED) in the caudate nucleus of adult, awake, male Sprague-Dawley rats. Compared to METH alone, extracellular DA release was prolonged for 140 min without changes in DA peak-effect by combined treatment with morphine/METH. Morphine did not change DOPAC efflux evoked by METH. On the other hand, both buprenorphine doses attenuated the METH-induced DA peak-effect. However, whereas high buprenorphine dose extended DA outflow for 190 min, the low-dose abbreviated DA release. High buprenorphine dose also shortened METH-induced decrease in DOPAC efflux. Data confirm that opiates modulate dopaminergic neurotransmission evoked by METH. Alteration of dopaminergic response to METH challenge under buprenorphine may suggest effectiveness of buprenorphine treatment in METH addiction.
Pereira
Frederico C
FC
Institute of Pharmacology and Therapeutics, Biomedical Institute for Research in Light and Image, Faculty of Medicine, University of Coimbra, Subunit 1-Polo 3, Azinhaga de Santa Comba, Celas, 3000-354 Coimbra, Portugal. fredcp@ci.uc.pt
Gough
Bobby
B
Macedo
Tice R
TR
Ribeiro
Carlos F
CF
Ali
Syed F
SF
Binienda
Zbigniew K
ZK
D000818:Animals; D002047:Buprenorphine / Q000378:metabolism / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology*; D008297:Male; D008694:Methamphetamine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002047:Buprenorphine; D008694:Methamphetamine; D004298:Dopamine