Alcohol Abuse

The potential utility of delta antagonists for the treatment of alcohol abuse has excited considerable interest over the last decade for at least two reasons. First, numerous studies suggest that the abuse-related effects of alcohol are mediated, at least in part, by endogenous opioid systems [114]. Second, the relatively nonselective opioid antagonist naltrexone has acknowledged clin-

TABLE 2 Summary of Delta Opioid Antagonist Effects on the Reinforcing Effects of Ethanol

Delta antagonist (dose/route)

Species3

Procedure (reinforcers

Effect on

H20 DepL EtOH SAd Selectivity6

Ref.

Studies showing a selective ICI174864

(0.5-3 mg/kg IP) Naltrindole

(10 mg/kg SC) ICI174864

(3-8 mg/kg SC) Naltrindole

(5-20 mg/kg IP) Naltriben

(0.375-6 mg/kg IP) Naltriben

(0.375-6 mg/kg IP) Naltriben

(0.375-6 mg/kg IP) ICI174864

(0.1 mg/kg IP) Naltrindole

(0.6-4 mg/kg SC) Naltrindole

delta antagonist-induced decrease in ethanol self-administration HAD rats 2-Bottle choice Yes Decrease

10% EtOH/water C57 mice 2-Bottle choice

12% EtOH/water P rats 2-Bottle choice

10% EtOH/water P rats 2-Bottle choice

10% EtOH/water P rats 2-Bottle choice

10% EtOH/water P rats 2-Bottle choice

10% EtOH + Sacc/Sacc P rats 2-Bottle choice

10% EtOH + Quin/Quin SD rats 2-Bottle choice

5% EtOH/water SD rats 2-bottle choice

5% EtOH/water P rats 2-Operandum operant

10% EtOH/Sacc W rats 2-Operandum operant

10% EtOH/water W rats 2-Operandum operant

10% EtOH/water

No Decrease

No Decrease

No Decrease

No Decrease

No Decrease

No Decrease

Yes Decrease

Yes Decrease

No Decrease

No Decrease

No Decrease1

>3-fold Not reported >2.7-fold >4-fold >l-fold >l-fold >l-fold >l-fold >3-fold 4.4-fold >l-fold Not reported

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