Naltrexone (NTX) is a nonspecific opioid antagonist that binds to mu‐, kappa‐, and delta‐opioid receptors. Previous research has demonstrated that rats given chronic, intermittent sucrose access have increased endorphin function. We have shown that rats given chronic, intermittent sucrose can discriminate 1.0 mg/kg NTX from saline in a two‐lever, operant choice procedure. We wondered if NTX's discriminative stimulus effects were mediated by kappa‐opioid receptors. To examine this possibility, we tested the effects of the kappa‐opioid agonist U69,593 in our discrimination procedure. Male Sprague‐Dawley rats were given access to 12‐hour access to a 25% sucrose solution and trained to discriminate NTX (1.0 mg/kg) from saline. Once discrimination criteria (80% or greater condition‐appropriate responding for 8 of 10 consecutive sessions) were reached, generalization testing began. We used a cumulative dosing procedure to determine if U69,593 alters the ability of NTX to produce its discriminative stimulus effects. Subjects were pretreated with U69,593 (0.0001 mg/kg – 0.1 mg/kg, s.c.) followed by increasing doses of NTX (0.001 mg.kg – 10.0 mg/kg, s.c.). Fifteen to 30 minutes after the injection, a test session began. Injections continued until response rates were suppressed or 10.0 mg/kg NTX was administered. Reversal tests were also conducted. During these tests, the training dose of NTX was administered and a test session began 15 minutes later. Then a single dose of U69,593 (0.001 mg/kg – 0.1 mg/kg, s.c.) was administered, followed by test sessions 15 to 120 minutes after the injection. U69,593 did not significantly alter the discriminative stimulus effects of NTX. This suggests that kappa‐opioid receptor antagonism is not sufficient to produce NTX's discriminative stimulus effects in rats given chronic, intermittent sucrose access.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Chronic, intermittent sucrose access has been shown to induce neurochemical changes in the brain, including increasing the levels of dopamine and D3‐receptor mRNA, decreasing the levels of D2‐receptor mRNA, and increasing μ‐opioid receptor binding. We wondered if chronic, intermittent sucrose consumption would alter the ability of rats to discriminate drugs that affect endorphin and dopamine functioning. We successfully trained rats with chronic, intermittent sucrose access to discriminate various naltrexone training doses (ranging from 0.32 – 3.2 mg/kg) from saline. In the present series of studies, we sought to determine if chronic, intermittent sucrose consumption alters the ability of haloperidol to serve as a discriminative stimulus. Sprague‐Dawley rats were trained to discriminate between haloperidol [0.018–0.56 mg/kg, 30 min pretreatment (PT)] and vehicle in a two‐lever, operant choice procedure. Most subjects reached the discrimination criteria (80% or greater condition‐appropriate responding for 8 of 10 consecutive sessions). Among subjects that acquired the discrimination, there were no significant differences in acquisition between subjects with chronic, intermittent sucrose access and subjects with 24‐hr water access. Haloperidol (0.032 – 0.056 mg/kg) produced significant rate suppression. Increasing the PT to 60 minutes increased rates of lever pressing and reinforcers earned, but did not alter haloperidol generalization functions. Taken together, chronic sucrose consumption enhanced naltrexone's ability to function as a discriminative stimulus, but did not affect the discriminative stimulus effects of haloperidol.Support or Funding InformationUniversity of Wisconsin‐Eau Claire Office of Research and Sponsored ProgramsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

No abstract