Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone

Abstract

Repeated intermittent exposure to psychostimulants was found to produce behavioral sensitization. The present study was designed to establish a mouse model and by which to investigate whether opioidergic system plays a role in methamphetamine-induced behavioral sensitization. Mice injected with 2.5 mg/kg of methamphetamine once a day for 7 consecutive days showed behavioral sensitization after challenge with 0.3125 mg/kg of the drug on day 11, whereas mice injected with a lower daily dose (1.25 mg/kg) did not. Mice received daily injections with either 1.25 or 2.5 mg/kg of methamphetamine showed behavioral sensitization after challenge with 1.25 mg/kg of the drug on days 11, 21, and 28. To investigate the role of opioidergic system in the induction and expression of behavioral sensitization, long-acting but non-selective opioid antagonist naltrexone was administrated prior to the daily injections of and challenge with methamphetamine, respectively. Our results show that the expressions of behavioral sensitization were attenuated by pretreatment with 10 or 20 mg/kg of naltrexone either during the induction period or before methamphetamine challenge when they were tested on days 11 and 21. These results indicate that repeated injection with methamphetamine dose-dependently induced behavioral sensitization in mice, and suggest the involvement of opioid receptors in the induction and expression of methamphetamine-induced behavioral sensitization.

Food-Induced Behavioral Sensitization, Its Cross-Sensitization to Cocaine and Morphine, Pharmacological Blockade, and Effect on Food Intake

“…Pretreatment with the opiate antagonist naltrexone abolished food-conditioned activity in FR animals, whereas it had little effect on the activity of controls, suggesting that opioid receptors are involved in the expression of food-induced sensitization. We are unaware of data on the effects of opioid blockade on the expression of cocaine sensitization, although naltrexone blocks the expression of behavioral sensitization to methamphetamine (Chiu et al, 2005). The ability of another opioid antagonist, naloxone, to decrease operant responding for food reinforcers (Glass et al, 1999) and food-conditioned locomotor activity in the presence of food (Hayward and Low, 2005), as well as the ability of the -agonist morphine to induce context-dependent conditioned feeding (Kelley et al, 2000) suggests a role for opiate receptors in food-conditioned responses.…”

Neurotoxic Effects of Methamphetamine on Rat Hippocampus Pyramidal Neurons

“…It is well known that repeated use of MAP induces addiction (Hyman 1996), sensitization (Chiu et al 2005;Shuto et al 2006), and those may cause deficits in memory and learning (Vorhees et al 2007;Lundqvist 2005). The major toxic effects of MAP involve disturbance of dopaminergic pathways (Daberkow et al 2005;Kish 2008;Gerra et al 2003), which leads to behavioral sensitization, which is a progressive and enduring increase in locomotor activity coupled with stereotypic behavior (Robinson and Becker 1986).…”

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

“…Naltrexone (NTX) is an opioid receptor antagonist with empirically supported efficacy and FDA approval for the treatment of alcoholism (Anton et al, 2006;O'Malley et al, 1992;Volpicelli et al, 1992) and opioid dependence (Cornish et al, 1997). Preclinical models suggest that NTX may also affect MA use, as NTX attenuated MA-induced sensitization (Chiu et al, 2005), amphetamine drug-seeking reinstatement (Haggkvist et al, 2008), and cue-induced MA seeking in rodents (Anggadiredja et al, 2004). In particular, preclinical studies suggested that μ-opioid (Chiu et al, 2006) and δ-opioid (Suzuki et al, 1997) receptors may underlie MA-induced behavioral sensitization, analogous to compulsive drug-seeking behavior in humans (ie, drug craving; Itzhak and Ali, 2002), through its modulatory actions of the mesolimbic dopamine system (Ford et al, 2006).…”