No abstract

Two methods were used to assess nicotine-induced antinociception: tail withdrawal from a hot water bath and hind paw withdrawal from a hotplate. Nicotine doses which produced 75-80% maximum response were 0.75 mg/kg (free base) for tail withdrawal and 0.35 mg/kg for paw withdrawal. The peripheral blocker chlorisondamine (0.1 mg/kg, SC) and the central antagonist, mecamylamine (1 mg/kg, SC) were each effective in blocking nicotine-induced increases in tail withdrawal latencies, suggesting that this effect of nicotine depends on either the action of nicotine at peripheral receptors or the functional integrity of those receptors. In contrast, nicotine-induced increases in paw withdrawal latencies were blocked by mecamylamine but not by chlorisondamine, even at other agonist/antagonist dose combinations. The results indicate that these two effects of nicotine involve at least partially separate pathways and may reflect a different mix of the antinociceptive and motor depressing effects of nicotine.

Alcohol consumption acutely increases smoking behavior, but the reverse relationship, the acute effects of smoking on alcohol intake, largely has been ignored. We examined whether smoking acutely increases the reinforcing value of alcohol, first in the absence of recent alcohol intake and then following an alcohol pre-load. Healthy, social-drinking smokers (n = 11 men, 14 women) engaged in a computerized task involving concurrent schedules of reinforcement for beer (FR10, 3 oz (90 ml) per reinforcement) or money (FR5 to FR30, $0.20 per reinforcement) during two sessions, one following day-long ad lib smoking and the other following overnight smoking abstinence. During each session, subjects performed the task in two sets of trials, one before and one after consumption of an alcohol pre-load, with 60 min between sets. To standardize the alcohol pre-load, all subjects were led to believe that they had earned 9 oz (270 ml) of beer after the first trial set, which they then consumed before the second set of trials. Compared to responding during the abstinent session, responding for alcohol during the smoking session was no different before the alcohol pre-load (trial set one) but was significantly greater following the alcohol pre-load (trial set two), although only in men and not women. Subjective sedation after the alcohol pre-load was attenuated during the smoking session in both men and women, but attenuated sedation due to smoking was related to subsequent alcohol-reinforced responding only in men. Additional research is needed to determine the extent to which these effects in men are pharmacological in nature or are conditioned responses to smoking or to consuming a preferred alcoholic beverage.

Smokers often report that the first cigarette of the day is the most rewarding, and subsequent smoking is less rewarding. Reduction in smoking enjoyment later in the day may be related to acute tolerance to the discriminative stimulus effects of nicotine. We examined changes in nicotine discrimination behaviour in humans as a function of acute nicotine pretreatment. Male and female dependent smokers (n = 15) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0 microg/kg) without nicotine pretreatment. They then were tested on generalization of discrimination across a range of spray doses from 0-20 microg/kg following pretreatment with placebo, moderate dose (14-21 mg) or high dose (28-42 mg) transdermal nicotine. Generalization testing involved both two- and three-response ('novel' option) quantitative procedures. Subjects also engaged in a self-administration phase at the end of each session, involving choices between nicotine (20 microg/kg) and placebo spray. Nicotine pretreatment significantly attenuated nicotine-appropriate responding at higher nicotine spray doses, suggesting acute tolerance, but only in women. Similar results were seen for subjective 'head rush', suggesting this effect may be related to discrimination behaviour in women. However, nicotine pretreatment also increased novel-appropriate responding, especially in men, following intermediate generalization doses, suggesting qualitatively different stimulus effects. Although differences were not significant, nicotine self-administration tended to be inversely associated with nicotine pretreatment dose in men but not in women. These results only modestly support the notion of acute tolerance to the discriminative stimulus effects of nicotine, and even then only in women and not in men.

Alcohol intake may acutely alter the discriminative stimulus and subjective effects of nicotine, perhaps explaining why alcohol increases tobacco smoking. In this study, cigarette smokers were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo. Three sessions then followed, in which the generalization of nicotine discrimination was tested across a range of doses (0--20 microg/kg) following pre-treatment with 0, 0.4, and 0.8 g/kg alcohol p.o. Intermittent 'topping' doses of alcohol maintained a steady breath alcohol level (BAL) throughout testing. Generalization testing involved both two- and three-choice ('novel' option) procedures. A visual discrimination task was also conducted to determine the specificity of effects of alcohol. Subjective and cardiovascular measures were obtained concurrent with discrimination responding. The relative reinforcing effects of nicotine were assessed after the end of generalization testing using a choice procedure. Alcohol pre-treatment had no significant effects on nicotine discrimination or self-administration behavior. Alcohol and nicotine each influenced selected subjective responses and heart rate, but virtually no interactions between the drugs were observed. Within the limitations of this study, these results do not support the notion that alcohol acutely alters nicotine's discriminative stimulus, subjective, or relative reinforcing effects at these low nicotine doses. Acute effects of alcohol on smoking behavior may be due to alterations in other effects of nicotine intake or in non-nicotine effects of tobacco smoking.