Dose-response analyses of associative tolerance to nicotine analgesia in the rat: Tail-flick and hot-plate tests.

Abstract

This study is the first to demonstrate associative tolerance to nicotine's analgesic effects as a shift in the dose-response curve (DRC) to the right. The subjects were 43 experimentally naive, male Sprague Dawley rats (Rattus norvegicus) randomly assigned to 2 groups. Home cage rats (HC; n = 21) received a series of 1 mg/kg nicotine doses explicitly unpaired with the distinctive context, whereas distinctive context rats (DC; n = 22) were injected with nicotine explicitly paired with the distinctive context. Rats in each of the 2 groups were randomly assigned to 1 of 3 nicotine testing doses to construct DRCs. The DRC of the rats that received nicotine in the distinctive context was shifted to the right of the DRC of rats that had had as much exposure to nicotine but had never experienced nicotine in the distinctive context. DC rats required nearly twice as much nicotine as HC rats to produce the same DRC. The discussion describes the implications of the results for theories of drug tolerance and nicotine addiction.

Plasma corticosterone in the rat in response to nicotine and saline injections in a context previously paired or unpaired with nicotine

“…Cepeda-Benito et al 2000). Like Cepeda-Benito et al (2000), we conducted mock-tail flick tests after 4 and 13 min post-injection, but substituted the 8-min mock tailflick test for a mock tail-bleed starting at 6 min postinjection.…”

“…Cepeda-Benito et al 2000). Like Cepeda-Benito et al (2000), we conducted mock-tail flick tests after 4 and 13 min post-injection, but substituted the 8-min mock tailflick test for a mock tail-bleed starting at 6 min postinjection. The mock tail-bleed consisted in massaging the tip of the rats' tail for 60 s. Mock tail-bleed tests were conducted to habituate the animals to these procedures to reduce stress reactivity on test day.…”

“…The pH of the nicotine solution was adjusted to 7.4 with a sodium hydroxide solution (1 N). Using this dose, we have found robust evidence of associative tolerance to nicotine's analgesic effects (Cepeda-Benito et al 1998, 2000. All nicotine and vehicle solutions were subcutaneously injected in the scruff of the neck of the subject (1.0 ml/kg of body weight).…”

“…The study followed procedures shown to produce robust associative tolerance to nicotine's analgesic effects (e.g., Cepeda-Benito et al, 1998, 2000. Animals received nicotine injections either explicitly paired or unpaired with a distinctive context.…”

Associative and behavioral tolerance to the analgesic effects of nicotine in rats: tail-flick and paw-lick assays

“…Although the phenomenology of drug tolerance has been extensively investigated with morphine and alcohol, research on the development of associative tolerance to nicotine's effects has been scarce (see Cepeda-Benito et al 2000). To date, there has not been any direct comparison between associative tolerance and behavioral nicotine tolerance phenomena or any systematic parametric research on the variables known to influence associative tolerance development to the effects of nicotine.…”