Actions of nicotine on the acquisition of an autoshaped lever-touch response in rats

Abstract

Experimentally naive male, Sprague-Dawley rats maintained at 85% of their original body weight were trained to touch a retractable lever that was presented on a random interval 48-s schedule. The lever retracted when touched or after 15 s had elapsed, and one 45 mg food pellet was delivered simultaneously with lever retraction or after an 8-s delay. Rats received ten daily sessions each consisting of ten lever presentations. Nicotine (0.25-0.8 mg/kg SC) administration, either 15 min prior to (pre-session) or immediately after (post-session) the daily autoshaping sessions, caused a significant dose-related impairment of acquisition with the post-session injections having the greater effect. Low doses of nicotine (0.025-0.1 mg/kg SC) had little effect on acquisition when injected pre-session or post-session. Injections of 0.45 mg/kg nicotine either immediately (t = 0) or at +5 min after the daily sessions impaired acquisition of the lever-touch response. Nicotine injected at +15, +30, +60, or +120 min had no effect on acquisition. A single intraventricular injection of the ganglionic blocker chlorisondamine (5 micrograms) 2 weeks prior to autoshaping blocked the impairment produced by 0.45 mg/kg nicotine. Post-session injections of nicotine did not alter the lever-touch behavior of well-trained animals, but suppressed responding in animals that were partially trained. Thus, nicotine-induced impairment of the autoshaped lever-touch response is dose dependent, centrally mediated, occurs within 5 min of a SC injection, and may interfere with post-training consolidation processes.

Blockade of nicotinic receptor‐mediated release of dopamine from striatal synaptosomes by chlorisondamine administeredin vivo

“…The long-lasting central blockade by CHL is well documented in in vivo studies using behavioural testing (Clarke & Kumar, 1983;Clarke, 1984;Reavill et al, 1986;Fudala & Iwamoto, 1987;Kumar et al, 1987;Mundy & Iwamoto, 1988;Corrigall et al, 1992;Clarke et al, 1994). Here, we demonstrate for the first time that in vivo administration of CHL results in ex vivo blockade, using an in vitro assay of brain nicotinic receptor function.…”

“…Studies in rats have shown that central administration of CHL (5 or 10 gg kg-' i.c.v.) results in a blockade of a variety of behavioural effects of nicotine that are mediated via CNS nicotinic receptors (Clarke & Kumar, 1983;Clarke, 1984;Reavill et al, 1986;Fudala & Iwamoto, 1987; Kumar et al, 1987;Mundy & Iwamoto, 1988;Corrigall et al, 1992). This blockade is remarkably persistent, lasting at least 5 weeks after a single administration of CHL (Clarke, 1984).…”

The pharmacology of the nicotinic antagonist, chlorisondamine, investigated in rat brain and autonomic ganglion

“…Such effects include locomotor stimulation and locomotor depression (Clarke, 1984), depression of operant behaviour and the nicotine cue (Kumar et al, 1987), conditioned taste aversion (Reavill et al, 1986), conditioned place aversion (Fudala & Iwamoto, 1987), nicotineinduced impairment of autoshaping response (Mundy & Iwamoto, 1988), and nicotine intravenous self-administration (Corrigall et al, 1992 Could chlorisondamine have destroyed a population of neurones which, though small, may be crucial for the mediation of the behavioural effects of nicotine? The extensive nature of our survey, in which one thousand brain sections were processed and examined, makes this possibility unlikely.…”

“…Consistent with its bisquaternary structure, chlorisondamine does not appear to penetrate the CNS readily. However, behavioural studies in rats have shown that chlorisondamine, when administered centrally, exerts an extremely long-lasting blockade of the central actions of nicotine (Clarke & Kumar, 1983;Clarke, 1984, Reavill et al, 1986Fudala & Iwamoto, 1987;Kumar et al, 1987;Mundy & Iwamoto, 1988;Clarke & Fibiger, 1990;Corrigall et al, 1992). For example, a single administration of chlorisondamine (0.2-5.Q0fg, i.c.v.…”

Blockade of nicotinic receptor‐mediated release of dopamine from striatal synaptosomes by chlorisondamine and other nicotinic antagonists administered in vitro

“…The bisquaternary structure of CHL appears to impede passage across the blood brain barrier, but a single administration of the drug, given either directly into the cerebral ventricles or in a sufficiently high dose systemically, results in a pharmacologically selective and remarkably persistent (several weeks) blockade of central actions of nicotine (Clarke & Kumar, 1983;Clarke, 1984;Reavill et al, 1986;Fudala & Iwamoto, 1987;Kumar et al, 1987;Mundy & Iwamoto, 1988;Clarke & Fibiger, 1990;Corrigall et al, 1992;Clarke et al, 1994). In contrast, ganglionic blockade induced by CHL is transient (Grimson et al, 1955;Plummer et al, 1955;Schneider & Moore, 1955;Clarke et al, 1994).…”