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  • 1
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Mecamylamine ; Tolerance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chronic injections of nicotine in rats produce upregulation of nicotinic cholinergic receptors. It has been proposed that this upregulation is a reflection of receptor desensitization and is the basis of functional tolerance. Mecamylamine, a non-competitive antagonist that blocks activation of nicotinic receptors, does not prevent upregulation produced by nicotine injections. This suggests that receptor activation is not a prerequisite for nicotine-induced receptor upregulation. Therefore, the present experiments tested whether mecamylamine would also fail to prevent the development of tolerance to nicotine. Six daily pairings of mecamylamine (1 mg/kg SC) with nicotine did block the development of tolerance to nicotine-induced antinociception (0.35 mg/kg) and to the ability of nicotine to suppress milk intake (0.66 mg/kg). In another experiment, six daily injections of mecamylamine, when given alone, did not alter the effects of a subsequent, acute injection of nicotine (0.35 mg/kg) in inducing antinociception in rats. There was no evidence that after six pairings of mecamylamine with nicotine, the cues associated with mecamylamine delivery took on conditioned antagonistic properties. These findings suggest that, unlike the receptor upregulation that results from either continuous or repeated nicotine administration, the tolerance following a short series of intermittent nicotine injections is dependent on receptor activation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Nicotine ; Conditioning ; Tolerance ; Analgesia ; Corticosterone ; Stress ; Conditioned tolerance ; Adrenocortical
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have shown that conditioned tolerance develops to some of the behavioral and endocrine effects of nicotine in rats. Other investigators have suggested that tolerance to multiple nicotine injections in mice may be due, in part, to elevated plasma corticosterone (CORT) levels, since repeated nicotine injections are associated with elevated CORT,chronically elevated CORT reduces nicotine responsiveness and adrenalectomy disrupts nicotine tolerance. Three experiments tested the feasibility of this hypothesis, as a mechanism for conditioned nicotine tolerance in rats, by determining whetheracute administration of CORT or manipulations that increase adrenocortical activity reduce nicotine responsiveness. In experiment 1, male rats were injected IP with CORT (1 mg/kg), vehicle (ETOH + distilled water) or no injection 10 min before nicotine (0.75 mg/kg, SC) and tested for nicotine-induced analgesia every other day for 10 days. A significant reduction in withdrawal latencies was obtained for CORT pretreated rats compared to animals given only nicotine. A similar reduction was produced by the vehicle pretreatment, which itself induced an elevation of endogenous CORT. Experiments 2 and 3 established that similar effects could be produced by doses of CORT as low as 0.125 mg/kg or by exposure to a novel environment which also elevated CORT levels. Results also suggest that a conditioned release of endogenous CORT was triggered by stimuli associated with nicotine delivery. These data are consistent with the hypothesis that a conditioned release of CORT could contribute to the development of tolerance to some of nicotine's effects. The possibility that other neuroendocrine mediators might be involved in addition to or instead of CORT, is also discussed.
    Type of Medium: Electronic Resource
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