Subject(s)
Alcoholism/prevention & control , Mass Screening , Prescription Drug Misuse/prevention & control , Referral and Consultation , Substance-Related Disorders/therapy , Aged , Aged, 80 and over , Alcoholism/therapy , District of Columbia , Female , Humans , Illicit Drugs , Male , Middle Aged , Substance-Related Disorders/prevention & control , Surveys and QuestionnairesABSTRACT
BACKGROUND: Despite synergistic increases in risks of various cancers, the incidence of concomitant smoking and drinking remains high. An additive or synergistic analgesic effect of combined alcohol and nicotine may contribute to their coabuse. Recently, we provided evidence that doses of alcohol and nicotine that are ineffective in inducing an antinociceptive effect alone, when combined, can induce such an effect. Moreover, this antinociceptive effect could be attenuated by pretreatment with the nonselective opioid antagonist naloxone. The purpose of this study was to determine the role of selective opioid receptor subtypes (micro, delta, and kappa) in mediating the antinociceptive effects of alcohol, nicotine, and their combination. METHODS: Adult male Wistar rats were administered selective opioid antagonists, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP, for micro receptor, 1.0 mg/kg), naltrindole (for delta receptors, 10 mg/kg), and norbinaltorphimine (nor-BNI, for kappa receptor, 10 mg/kg) before injection of alcohol, nicotine or their combination. The animals were tested in hot-plate and tail-flick assays, representing nociception mediated predominantly via brain or spinal pathways, respectively. All the injections were administered acutely and the nociceptive tests were carried out 20 minutes after alcohol and 10 minutes after nicotine administration. RESULTS: In general, the antagonists were more effective in blocking the effects of alcohol, nicotine, or their combination in the tail-flick versus the hot-plate assay. CTAP was most effective in blocking the effects of alcohol alone and nicotine alone in the tail-flick test, whereas in the hot-plate test both CTAP and naltrindole were more effective than nor-BNI. All 3 antagonists had a very similar profile in attenuating the combination of alcohol and nicotine effect in the hot-plate assay. None of the antagonists had a significant effect against the highest alcohol-nicotine dose in this test. In the tail-flick test, however, CTAP and naltrindole were more effective than nor-BNI in attenuating the highest alcohol-nicotine dose. CONCLUSIONS: The data suggest the utility of all 3 opioid antagonists in blocking the effects of alcohol, nicotine, or their combination in spinally mediated antinociception. Although the supraspinally mediated antinociception was also attenuated by the opioid antagonists, further investigation of combination doses of these antagonists in fully blocking the supraspinal effects or attenuating voluntary alcohol and nicotine intake is warranted.
Subject(s)
Analgesics , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Narcotic Antagonists , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Animals , Hot Temperature , Male , Naltrexone/analogs & derivatives , Naltrexone/pharmacology , Narcotic Antagonists/pharmacology , Pain Measurement/drug effects , Peptide Fragments , Peptides/pharmacology , Rats , Rats, Wistar , Reaction Time/drug effects , Receptors, Opioid, delta/drug effects , Receptors, Opioid, kappa/antagonists & inhibitors , Receptors, Opioid, mu/antagonists & inhibitors , SomatostatinABSTRACT
Both alcohol and nicotine have been shown to possess antinociceptive or analgesic effects. An additive or synergistic antinociceptive effect induced by simultaneous administration of alcohol and nicotine could further contribute to their co-abuse. In this study, we sought to evaluate the antinociceptive effects of various combinations of ethanol and nicotine and to determine whether these effects could be blocked by an opioid antagonist. Adult male Wistar rats were treated with various doses of alcohol (0.1-2 g/kg), nicotine (0.01-2 mg/kg) or their combination and their behavior in tail flick test, reflective of spinal antinociception and hotplate test, mainly reflective of supraspinal antinociception were evaluated. Alcohol at the highest dose of 2 g/kg resulted in significant antinociceptive effects in both assays. Nicotine at 1 mg/kg resulted in significant antinociception in the hotplate; however, in the tail flick test a dose of 2 mg/kg was required for an antinociceptive effect. Combination of doses of alcohol and nicotine that were ineffective by themselves resulted in antinociceptive responses in both paradigms. These effects were attenuated by pretreatment with the non-selective opioid receptor antagonist naloxone. The data indicate that a combination of alcohol and nicotine can result in a synergistic antinociceptive response that is at least partially mediated by the opioid system. The analgesic effects induced by combination of alcohol and nicotine may be a contributory factor in their co-abuse.
