Discriminative stimulus properties of muscarinic agonists

Abstract

In a two-lever, food-reinforced drug-discrimination paradigm separate groups of rats were trained to discriminate either arecoline, pilocarpine or oxotremorine from saline. The discriminative cues of all three agonists were potently blocked by scopolamine, but only by 30-60 fold higher doses of methylscopolamine. The three agonists all suppressed overall response rate. These rate-suppressant effects were not blocked by scopolamine in doses which blocked the discriminative cues. In generalization tests, arecoline elicited selection of the drug-appropriate lever in all groups of trained animals. Pilocarpine was discriminated as drug by all pilocarpine-trained animals and by a majority of oxotremorine-trained animals, but was not significantly discriminated by the arecoline-trained group. Oxotremorine was discriminated by all oxotremorine-trained animals but only by some pilocarpine-trained animals, and was not significantly discriminated by the arecoline-trained group. Morphine, haloperidol, chlordiazepoxide, pentobarbital and nicotine were not generalized to any of the training drugs. The discriminative stimuli produced by the training drugs are therefore specific and exhibit properties indicative of an origin at central muscarinic receptors but may not be identical.

Nicotinic aspects of the discriminative stimulus effects of arecoline

“…The subsequent finding that nicotine produced arecoline-like discriminative stimulus effects in these rats (Fig. 2) was surprising, particularly because in previous studies of arecoline's discriminative stimulus effects (Jung et al,1987;Meltzer and Rosecrans, 1981) nicotine did not produce arecoline-appropriate responding. Slightly larger training doses of arecoline (1.5 mg/kg and 1.74 mg/kg, respectively) were used in these studies, but it is unlikely that this accounts for the discrepancy between the current work and the earlier studies.…”

“…Behavioral studies of interactions between arecoline and nicotine are limited but generally have not supported a nicotinic component of arecoline's actions. Nicotine was found to produce no arecoline-like discriminative stimulus effects in rats trained to discriminate arecoline (Meltzer and Rosecrans, 1981;Jung et al, 1987). Similarly, the cholinesterase inhibitor, physostigmine showed discriminative stimulus properties in common with arecoline, but not with nicotine (Meltzer and Rosecrans, 1988).…”

Pharmacological characterization of the physostigmine stimulus in rats

“…The procedure used in the present experiment has been described elsewhere (Jung et al 1987b). Briefly, materials consisted of standard Skinner Boxes, fitted with two levers and a food cup, monitored by Apple II microcomputers.…”

Neuropharmacology of the Interoceptive Stimulus Properties of Nicotine

“…The classical central nAChR antagonists mecamylamine and dihydro-β-erythroidine (DHβE) block nicotine discrimination completely without disrupting response rates, whereas the mAChR antagonist atropine fails to block the nicotine cue [11, 13, 21, 27, 29–31]. Nicotine also fails to generalize to the S D effects of the mAChR agonists arecoline, physostigmine, pilocarpine or oxotremorine [32–35] or the S D effects of the mAChR antagonist scopolamine [36]; physostigmine also fails to alter the nicotine cue [37]. …”