Post-treatment of dextromethorphan on methamphetamine-induced drug-seeking and behavioral sensitization in rats.
In our previous study, we first demonstrated a significant effect of dextromethorphan (DM) on morphine-seeking behavior in morphine-dependent rats, when DM was given during morphine withdrawal. Using the same conditioned place preference (CPP) paradigm modified for measuring drug-seeking-related behavior, we further investigated the possible effect of DM on methamphetamine (MA)-seeking in MA-dependent rats. Our data showed that DM could also effectively suppress the drug-seeking behavior for MA, when administered during MA withdrawal. This suggests that DM may possess a pharmacological property to prevent drug-seeking behavior for addictive drugs in general. To examine the action sites of DM in the brain, DM was microinjected into the VTA or the NAc, and tested for its effect on MA-seeking during withdrawal. Both intra-VTA and intra-NAc injections of DM were able to block the MA-seeking, suggesting that DM has a dual action sites. In our neurochemical results, intra-NAc injection of DM showed a clear reduction of DA turnover rate at the NAc and the mPFC in response to MA challenge during withdrawal, which matched with the behavioral results. However, intra-VTA injection of DM reduced the DA turnover rate at the mPFC but did not have effect on the DA turnover rate at the NAc. Although further investigations may be needed to verify the connection between our neurochemical and behavioral results, the present study highlights the therapeutic potential of DM in antidrug-seeking behavior of MA and that the mechanism could be related to its effect on the mesolimbic and mesocortical dopaminergic pathways.
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Pao-Pao
PP
Yang
Eagle Yi-Kung
EY
Huang
Yu-Ying
YY
Fu
Tsai-Shan
TS
Ho
Pao-Luh
PL
Tao
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000187:drug effects
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D008694:Methamphetamine; D003915:Dextromethorphan; D004298:Dopamine