Effects of Nicotine and Epibatidine on Thermal Nociception and Prostaglandin E₂-Induced Thermal Hypersensitivity in Rhesus Monkeys

Authors: BRANDT M.R.; NEGUS S.S.

Source: Analgesia, Volume 5, Numbers 3-4, 2001 , pp. 239-247(9)

Publisher: Cognizant Communication Corporation

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Abstract:

Purpose. It has been suggested that nicotinic acetylcholine receptor agonists may produce clinically useful analgesic effects. To further evaluate this hypothesis, the present study compared the effects of the nicotinic agonists nicotine and epibatidine with the effects of the mu-opioid agonist morphine on schedule-controlled responding, thermal nociception, and thermal hypersensitivity in rhesus monkeys.

Results. In the assay of schedule-controlled responding, nicotine (0.1–3.2 mg/kg), epibatidine (0.00032–0.0032 mg/kg), and morphine (0.32–10.0 mg/kg) dose-dependently decreased response rates maintained under a fixed ratio 30 schedule of food presentation. High doses of nicotine and epibatidine also produced sedation in all monkeys and vomiting in some monkeys. In the assay of thermal nociception, neither nicotine (0.32–5.6 mg/kg) nor epibatidine (0.00032–0.0032 mg/kg) substantially altered tail-withdrawal latencies from 50°C water. In contrast, morphine (0.32–10.0 mg/kg) produced dose-dependent and maximal antinociceptive effects at doses similar to those that also decreased rates of schedule-controlled responding. Thermal hypersensitivity was induced by administration of prostaglandin E₂ (PGE₂; 0.0158 mg) into the tail, which decreased tail-withdrawal latencies from 18 s to less than 3 s in 46°C water. Nicotine (1.0–5.6 mg/kg) and epibatidine (0.00032–0.0032 mg/kg) reversed thermal hypersensitivity in one of three and two of three monkeys, respectively, and these effects were only observed at high doses that also produced sedation and vomiting. Morphine (0.1–1.0 mg/kg) dose-dependently reversed thermal hypersensitivity in all three monkeys at doses approximately five- to ninefold lower than those that decreased rates of schedule-controlled responding or produced thermal nociception.

Conclusions. These findings suggest that up to doses that produce adverse behavioral effects, nicotine and epibatidine produce only weak and inconsistent antinociceptive effects in rhesus monkeys.

Keywords: Nicotine Epibatidine Morphine Monkey Schedule-cont

Language: English

Document Type: Research article

Affiliations: 1: Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, Belmont, MA 02178-9106

Publication date: 2001-01-01

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