Acute stress or corticosterone administration reduces responsiveness to nicotine: implictions for a mechanism of conditioned tolerance

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 whether acute 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Mecamylamine prevents tolerance but enhances whole brain [ 3 H]epibatidine binding in response to repeated nicotine administration in rats

“…However the actions of MEC on NMDA receptors occur only at much higher doses than the 1 mg/kg used here McDonough and Shih 1995). Furthermore, there was no effect of multiple vehicle injections on antinociception in the present study, and other work indicates that stress decreases, rather than increases, the antinociceptive effects of NIC (Caggiula et al 1993; see also Flemmer and Dilsaver 1989).…”

Effects of continuous oral nicotine administration on brain nicotinic receptors and responsiveness to nicotine in C57Bl/6 mice

“…In spite of the failure of CNS nAChr receptor up-regulation, chronically injected mice develop a profound tolerance to nicotine that persists for an extended period of time following cessation of the chronic injection regimen (Pauly and Collins 1993). Previous studies have suggested that chronic nicotine injections in mice may produce a form of conditioned drug tolerance, unrelated to the specific pharmacological properties of nicotine Caggiula et al 1993). Mice chronically injected with nicotine also hypersecrete glucocorticoid hormones, which may themselves reduce sensitivity to nicotine (Pauly et al 1990(Pauly et al , 1993Grün et al 1992Grün et al , 1995Bouzart and Barrantes 1993;Caggiula et al 1993;Robinson et al 1996a).…”

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

“…In theory, associative forms of drug tolerance should involve the interaction of neural pathways involved in learning and memory with those responsible for the pharmacokinetic and pharmacodynamic changes that produce drug tolerance (Trujillo 2000). With regards to nicotine, researchers have proposed that conditioned activation of the hypothalamic-pituitaryadrenocortical system and conditioned release of corticosterone may mediate the development of associative nicotine tolerance (Pauly et al 1992;Caggiula et al 1993Caggiula et al , 1995. Circulating levels of corticosterone have been found to correlate with magnitude of nicotine tolerance (Pauly et al 1992), and environmental cues associated with nicotine delivery may elicit a conditioned corticosterone response (Caggiula et al 1993).…”