Minocycline, an antibiotic with inhibitory effect on microglial activation, attenuates the maintenance and reinstatement of methamphetamine-seeking behavior in rat.
Methamphetamine (METH) is a major criminal justice and public health problem. Repeated use of METH causes dependence in humans and there are currently no particular pharmacological treatments for METH addiction. Glial cell activation is linked with METH abuse and METH administration causes activation of these cells in many areas of the brain. Many studies have demonstrated that glial cell modulators can modulate drug abuse effects. In this study, we examined the effect of the putative microglial inhibitor, minocycline on maintenance and prime-induced reinstatement of METH seeking behavior using the conditioned place preference (CPP) paradigm. CPP induced with METH (1 mg/kg, i.p. for 3 days) lasted for 11 days after cessation of METH treatment and priming dose of METH (0.5 mg/kg, i.p.) reinstated the extinguished METH-induced CPP. Daily treatment of minocycline (40 mg/kg, i.p.) followed by establishment of CPP blocked the maintenance of METH-induced CPP and also could attenuate priming-induced reinstatement. Furthermore, daily bilateral intra-accumbal injection of minocycline (10 and 20 μg/0.5 μl saline), during extinction period blocked the maintenance of METH CPP but just the highest dose of that could attenuate priming-induced reinstatement. We showed that minocycline administration during extinction period could facilitate extinction and maybe abolish the ability of drug-related cues evoke reinstatement, suggesting that minocycline might be considered as a promising therapeutic agent in preventing relapse in METH dependent individuals.
Molecular Medicine Research Centre, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; Iran National Science Foundation, Tehran, Iran.
Ghassem
G
Attarzadeh-Yazdi
Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Reza
R
Arezoomandan
Iran National Science Foundation, Tehran, Iran; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Haghparast@yahoo.com.
Abbas
A
Haghparast
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D008911:Minocycline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D019966:Substance-Related Disorders / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D008911:Minocycline
Glial cell activity; Methamphetamine maintenance; Minocycline; Nucleus accumbens; Reinstatement