Further evidence for the mechanisms that may mediate nicotine discrimination

doi:10.1016/0091-3057(92)90231-4

Pharmacology Biochemistry and Behavior

Volume 41, Issue 4, April 1992, Pages 807-812

https://doi.org/10.1016/0091-3057(92)90231-4 Get rights and content

Abstract

Rats were trained to discriminate the interoceptive stimuli produced by subcutaneously administered 0.4 mg/kg nicotine in a two-lever, food-motivated, operant task. Once criterion performance was attained, dose-response experiments indicated an ED₅₀ value of 0.1 mg/kg and subsequent time course experiments showed a maximal effect between 10 and 30 min postadministration with a return to saline-like responding at 2 h. Pretreatment with the presynaptic dopamine release inhibitors CGS 10746B (30 mg/kg), as well as with the dihydropyridine calcium blocker isradipine (15 mg/kg), each produced a significant blockade of nicotine discrimination. In contrast, the 5-hydroxytryptamine (5-HT) receptor 5-HT₃ antagonist ICS-205930 did not produce any effect upon nicotine discrimination. Thus, drugs that interfere with calcium influx, viz., isradipine, or with dopamine release (CGS 10746B) also interfere with nicotine discrimination and these results suggest that calcium influx and dopamine release may be necessary conditions for nicotine discrimination.

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Rodents can be trained quickly to respond differentially under the influence of two or more contrasting interoceptive drug states that set the occasion for specific operant response → food-reinforcement or non-reinforcement contingencies that are conditionally in effect. Individually, the discriminative stimulus functions of nicotine and ethanol have been well documented (e.g., Barry, Koepfer, & Lutch, 1965; Barry & Krimmer, 1976; Gauvin, Youngblood, Goulden, Briscoe, & Holloway, 1994; Rosecrans & Villanueva, 1991; Schechter & Meehan, 1992; Schechter & Rosecrans, 1972; Stolerman, Garcha, Pratt, & Kumar, 1984; Troisi, 2003a,b; Troisi, 2006, 2011). However, far less is known about the discriminative stimulus functions of these two drugs in compound (see Troisi et al., 2013 for review; c.f., Ford, Davis, McCracken, & Grant, 2013; Ford, McCracken, Davis, Ryabinin, & Grant, 2012, for reports using mice, and see Randall, Cannady, & Besheer, 2016 for a Pavlovian evaluation).
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This chapter summarizes the current research and literature on nicotine and L-type calcium channels (LTCCs). It introduces the basic knowledge about LTCCs, including the nomination, structure, subunits and subtypes, distribution, and physiological properties. The fundamental neuronal circuits of nicotine addiction, especially the mesolimbic system and learning- or anxiety-related areas, are then briefly introduced, as well as how LTCC expression differs depending on the key brain area. Along with introducing current literature, behavioral studies are discussed including, but not limited to, the effects of LTCCs on nicotine exposure, including such behavioral tests as nociception, locomotion, sensitization, conditioned place preference, memory, anxiety, and conditioned place aversion involving the different stages of nicotine addiction: acquisition, expression, withdrawal, and reinstatement. Foremost, it introduces several possible underlying molecular pathway studies mediating the LTCC effects on nicotine in different involved brain areas, mainly in the cerebral cortex and the ventral tegmental area. Lastly, the current problems in these research areas are discussed and in what future directions we should peruse.
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The administration of 5-HT3-receptor antagonists did not block nicotine-induced hyperactivity [27,129]. The discriminative stimulus properties of nicotine do not depend on 5-HT3-receptor activation since they could not be blocked by a 5-HT3-receptor antagonist in rats [643]. Antagonists at the 5-HT3-receptor were found to block nicotine-induced CPP [95,96].
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Further evidence for the mechanisms that may mediate nicotine discrimination

Abstract

Life Sci.

Biochem. Pharmacol.

Eur. J. Pharmacol.

Brain Res.

Eur. J. Pharmacol.

J. Substance Abuse

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Life Sci.

The discriminative stimulus properties of cocaine: Effects of BAY K8644 and nimodipine

Eur. J. Pharmacol.

5-HT3 receptor antagonists block morphine- and nicotine- but not amphetamine-induced rewards

Psychopharmacology (Berl.)

A description of the nicotine stimulus and tests of its generalization to amphetamine

Psychopharmacology (Berl.)

Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rat

J. Pharmacol. Exp. Ther.

Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats

The importance of calcium in amphetamine-induced turning behavior in mice with unilateral nigro-striatal lesions

Neuropharmacology

5-HT₃ receptor antagonists block morphine- and nicotine- but not amphetamine-induced rewards