TY - JOUR
T1 - The selective μ opioid receptor antagonist β-funaltrexamine attenuates methamphetamine-induced stereotypical biting in mice
AU - Kitanaka, Junichi
AU - Kitanaka, Nobue
AU - Hall, F. Scott
AU - Uhl, George R.
AU - Fukushima, Yuko
AU - Sawai, Tatsuo
AU - Watabe, Kaname
AU - Kubo, Hitoshi
AU - Takahashi, Hitoshi
AU - Tanaka, Koh Ichi
AU - Nishiyama, Nobuyoshi
AU - Tatsuta, Tomohiro
AU - Morita, Yoshio
AU - Takemura, Motohiko
PY - 2013/7/19
Y1 - 2013/7/19
N2 - We investigated whether pretreatment with opioid receptor antagonists affected methamphetamine (METH)-induced stereotypy in mice. Pretreatment of male ICR mice with naloxone, a relatively non-selective opioid receptor antagonist, significantly attenuated the total incidence of METH-induced stereotypical behavior compared with saline vehicle-pretreated subjects. Furthermore, the distribution of METH-induced stereotypical behavior was affected by naloxone administration. Thus, METH-induced stereotypical sniffing and persistent locomotion were significantly increased by naloxone treatment while stereotypical biting was reduced. One way to interpret this pattern of effects is that pretreatment with naloxone appeared to produce a shift in the dose-response curve for METH. Thus, while the more intense forms of oral-facial stereotypies were reduced, increased persistent locomotion was observed in mice given naloxone followed by METH. The selective μ opioid receptor antagonist β-funaltrexamine, but not nor-binaltorphimine (a κ-selective antagonist) nor naltrindole (a δ-selective antagonist), mimicked the effect of naloxone. These observations suggest that opioid receptor antagonists may attenuate METH-induced stereotypical biting in mice via μ opioid receptors, and suggest that antagonism of this system may be a potential therapeutic approach to reducing some deleterious effects of METH use and perhaps in the treatment of some forms of self-injurious behavior.
AB - We investigated whether pretreatment with opioid receptor antagonists affected methamphetamine (METH)-induced stereotypy in mice. Pretreatment of male ICR mice with naloxone, a relatively non-selective opioid receptor antagonist, significantly attenuated the total incidence of METH-induced stereotypical behavior compared with saline vehicle-pretreated subjects. Furthermore, the distribution of METH-induced stereotypical behavior was affected by naloxone administration. Thus, METH-induced stereotypical sniffing and persistent locomotion were significantly increased by naloxone treatment while stereotypical biting was reduced. One way to interpret this pattern of effects is that pretreatment with naloxone appeared to produce a shift in the dose-response curve for METH. Thus, while the more intense forms of oral-facial stereotypies were reduced, increased persistent locomotion was observed in mice given naloxone followed by METH. The selective μ opioid receptor antagonist β-funaltrexamine, but not nor-binaltorphimine (a κ-selective antagonist) nor naltrindole (a δ-selective antagonist), mimicked the effect of naloxone. These observations suggest that opioid receptor antagonists may attenuate METH-induced stereotypical biting in mice via μ opioid receptors, and suggest that antagonism of this system may be a potential therapeutic approach to reducing some deleterious effects of METH use and perhaps in the treatment of some forms of self-injurious behavior.
KW - μ Opioid receptor
KW - Endogenous opioid system
KW - Methamphetamine
KW - Stereotypical behavior
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U2 - 10.1016/j.brainres.2013.05.027
DO - 10.1016/j.brainres.2013.05.027
M3 - Article
C2 - 23727404
AN - SCOPUS:84879798686
SN - 0006-8993
VL - 1522
SP - 88
EP - 98
JO - Brain Research
JF - Brain Research
ER -