Browsing by Author "Blair, Graham"
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Item Open Access Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats.(Psychopharmacology, 2020-06) Levin, Edward D; Wells, Corinne; Hawkey, Andrew; Holloway, Zade; Blair, Graham; Vierling, Alexander; Ko, Ashley; Pace, Caroline; Modarres, John; McKinney, Anthony; Rezvani, Amir H; Rose, Jed ERationale
A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine self-administration.Objectives
The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine self-administration would reduce opiate self-administration.Methods
Amitifadine, a triple reuptake inhibitor of dopamine, norepinephrine, and serotonin, was assessed in female Sprague-Dawley rats to determine whether it significantly reduces remifentanil self-administration with either acute or chronic treatment.Results
Acutely, amitifadine doses of 5, 10, and 20 mg/kg each significantly reduced remifentanil self-administration. In a chronic study, repeated treatment with 10 mg/kg of amitifadine continued to reduce remifentanil self-administration, even after the cessation of treatment. However, amitifadine was not found to attenuate the rise in remifentanil self-administration with continued access. This study and our earlier one showed that the 10 mg/kg amitifadine dose did not significantly affect food motivated responding. Amitifadine did not attenuate remifentanil-induced antinociception as measured on the hot plate test but extended and maintained antinociceptive effects.Conclusions
These studies show the promise of amitifadine as a treatment for countering opiate self-administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain.Item Open Access Correction to: Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats.(Psychopharmacology, 2021-04) Levin, Edward D; Wells, Corinne; Hawkey, Andrew; Holloway, Zade; Blair, Graham; Vierling, Alexander; Ko, Ashley; Pace, Caroline; Modarres, John; McKinney, Anthony; Rezvani, Amir H; Rose, Jed EOur article published in Psychopharmacology had a typographical error in the units of remifentanil infusion for selfadministration. The correct infusion dose of remifentanil is 0.3 µg/kg/infusion not 0.3 mg/kg/infusion.Item Open Access Dextromethorphan and bupropion reduces high level remifentanil self-administration in rats.(Pharmacology, biochemistry, and behavior, 2020-04) Blair, Graham; Wells, Corinne; Ko, Ashley; Modarres, John; Pace, Caroline; Davis, James M; Rezvani, Amir H; Rose, Jed E; Levin, Edward DOpiate addiction has risen substantially during the past decade. New treatments to combat opiate addiction are sorely needed. The current study was conducted to determine the acute individual and interactive effects of bupropion and dextromethorphan in a rat model of opiate self-administration using the short-acting synthetic opioid remifentanil. Both of these drugs have been found to reduce self-administration of nicotine. Bupropion and dextromethorphan and their combination had differential effects depending on whether the rats showed higher or lower baseline remifentanil self-administration. The rats with higher initial remifentanil self-administration showed a significant decrease in remifentanil self-administration with bupropion or dextromethorphan treatment, compared to the vehicle control condition. This decrease in self-remifentanil administration was most pronounced when combination of the higher doses of bupropion and dextromethorphan were administered. In contrast, the rats with lower baseline remifentanil self-administration showed the opposite effect of drug treatment with an increase in remifentanil self-administration with bupropion treatment compared to the vehicle control condition. Dextromethorphan had no significant effect inthis group. This study shows that combination bupropion and dextromethorphan affects remifentanil self-administration in a complex fashion with differential effects on low and high baseline responders. In subjects with high baseline remifentanil self-administration, bupropion and dextromethorphan treatment significantly reduced self-administration, whereas in subjects with low baseline remifentanil self-administration, bupropion increased remifentanil self-administration and dextromethorphan had no discernible effect. This finding suggests that combination bupropion-dextromethorphan should be tested in humans, with a focus on treating people with high-level opiate use.Item Open Access Differential behavioral functioning in the offspring of rats with high vs. low self-administration of the opioid agonist remifentanil.(European journal of pharmacology, 2021-10) Rezvani, Amir H; Wells, Corinne; Hawkey, Andrew; Blair, Graham; Koburov, Reese; Ko, Ashley; Schwartz, Andrea; Kim, Veronica J; Levin, Edward DOpioid use disorder (OUD) has a variety of adverse effects on both the users and their offspring. In the current study, a random group of Sprague-Dawley rats (25 females and 15 males) were tested for intravenous self-administration of the opioid agonist remifentanil to determine the range of acquisition for opioid. One-month after the end of self-administration of remifentanil, rats with the highest intake were mated together and rats with lowest intake were mated together. Then, the offspring of the two groups were tested for anxiety-like behavior, locomotor activity, nociception and intravenous remifentanil self-administration. The parents showed a range of remifentanil self-administration, especially in the female rats. The offspring of the parents with low and high remifentanil self-administration showed significant differences in specific behavioral functions. On the hotplate test of nociception, the female offspring parents with high remifentanil self-administration had significantly longer hotplate latencies, indicating reduced nociception, than the female offspring of parents with low remifentanil-self-administration, whereas there was no difference in the male offspring of low and high responding parents. In the elevated plus maze test of anxiety-like behavior, the offspring of the parents with high remifentanil intake showed more anxiety-like behavior than the offspring of the parents with low remifentanil intake regardless of sex. Locomotor activity was not significantly different. Interestingly, no significant differences in remifentanil self-administration in the offspring of parents with low and high remifentanil self-administration were detected. Overall, our data suggest a considerable range in remifentanil self-administration in rats and the offspring of rats with high opioid self-administration exhibit different behaviors vs offspring of rats with low opioid self-administration.