Involvement of the opioid system in the development and expression of sensitization to the locomotor-activating effect of ethanol

Abstract

Previous studies have shown that pretreatment with naloxone (Nlx), an opiate antagonist, attenuates the stimulating effect of ethanol. The purpose of the present study was to determine the influence of Nlx on the development and expression of the sensitization to ethanol. Initially, effects of different doses of Nlx on the response to a low dose of ethanol (2.0 g/kg) were assessed. Nlx (1.0 and 3.0 mg/kg i.p.) decreased the stimulating effect of ethanol. Groups of mice were treated with saline or Nlx (1.0 mg/kg i.p.) plus saline or ethanol (2.0 g/kg i.p.) during 21 d. On day 25 of treatment all animals received an ethanol challenge (2.0 g/kg i.p.). It significantly increased the locomotor activity of mice that had received chronic ethanol (2.0 g/kg) once daily as compared to those that had received saline. Chronic administration of Nlx (1.0 mg/kg i.p.), during the same period of time, did not change the locomotor activity of the mice. However, the group concomitantly treated with Nlx+ethanol did not develop sensitization to the locomotor-activating effect of ethanol. Another experiment was carried out to determine the effects of Nlx on the expression of sensitization to ethanol. Acute pretreatment with Nlx did not change the response of the mice that had developed sensitization to ethanol. These data show Nlx's prevention of the development of ethanol-induced sensitization but not of its expression, suggesting an important role of the opioid neurotransmitter systems modulating the development of sensitization to the locomotor-activating effect of ethanol.

The Role of Opioid Receptor Subtypes in the Development of Behavioral Sensitization to Ethanol

“…The role of specific subtypes of the mu opioid receptor (ie mu 1 + 2 or mu 3 ) in ethanol sensitization, however, appears to be limited; as we found that the functional relevance of these subtypes is restricted to the acute locomotor effects of ethanol. Data demonstrated robust sensitization to the locomotor activating effects of ethanol, as has previously been reported for Swiss mice (Camarini et al, 2000b;Miquel et al, 2003). Ethanol (2.5 g/kg) produced a significant increase in locomotor activity when acutely administered.…”

“…Male Swiss (IOPS Orl) albino mice, a strain chosen for its sensitivity to the stimulatory and sensitizing effects of ethanol (Camarini et al, 2000b;Miquel et al, 2003), were purchased from Janvier Spain, SA (Barcelona, Spain), housed (three per cage) and acclimated to the colony room for at least 2 weeks prior to study initiation. At the time of testing, mice were 6 weeks old.…”

“…A critical role of the opioid system in the sensitizing effects of ethanol in mice has recently been proposed (Camarini et al, 2000b;Miquel et al, 2003). Nonselective antagonism of opioid receptors with naloxone has been shown to block the development of ethanol sensitization (Camarini et al, 2000b).…”

“…Nonselective antagonism of opioid receptors with naloxone has been shown to block the development of ethanol sensitization (Camarini et al, 2000b). While both naloxone and naltrexone are characterized as nonspecific opioid receptor antagonists, they have been found to have a higher affinity for mu than for delta opioid receptors (Takemori and Portoghese, 1984;Williams et al, 2001).…”

“…Low doses of naloxone and naltrexone (eg 1 mg/kg and less) are suggested to be specific for the mu opioid receptor, whereas higher doses may additionally recruit delta opioid receptors (Mhatre and Holloway, 2003;Takemori and Portoghese, 1984). According to this, data from experiments showing a blockade of ethanol sensitization with opioid antagonists suggest that mu opioid receptors may be particularly involved in ethanol sensitization (Camarini et al, 2000b). However, the hypothesis that behavioral sensitization to ethanol is specifically achieved through mu opioid receptors needs to be assessed.…”