A Comparison of the Effects of Nicotine and (+)-Amphetamine on Rat Behaviour in an Unsignalled Sidman Avoidance Schedule

Abstract

In agreement with the results of previous studies, the withdrawal of nicotine from rats trained on an unsignalled Sidman avoidance schedule under the influence of the drug (0.4 mg kg-1 given subcutaneously 3 min before each training session) was associated with a reduction in lever-pressing responses (P less than 0.05) and an increase in the number of shocks received (P less than 0.01). The number of shocks received by the withdrawn rats was also greater (P less than 0.05) than the number of shocks received by rats trained and tested with saline, whereas the number of lever-pressing responses recorded for saline-treated rats was not influenced significantly by the drug used during training. The subcutaneous administration of (+)-amphetamine (0.5 mg kg-1 30 min before the test session) stimulated lever-pressing in rats trained with saline or nicotine and abolished the increase in the number of shocks received by the nicotine-withdrawn rats, but had no significant effect on the number of shocks received by rats trained with saline. The number of shocks received by the rats trained on the schedule with (+)-amphetamine but tested after an injection of saline was also greater (P less than 0.05) than the number of shocks received by rats trained and tested with saline. It is concluded that the disruption in shock avoidance performance observed for the nicotine- and (+)-amphetamine-withdrawn rats may reflect the development of dependence upon the stimulant properties of these drugs.

Dose, duration, and pattern of nicotine administration as determinants of behavioral dependence in rats

“…The disruption of operant behavior during withdrawal of drugs has been referred to as evidence of "behavioral dependence" upon drugs (Schuster and Thompson 1969). These findings support other published studies of nicotine dependence inferred from disruptions of operant behaviors following precipitated withdrawal or abstinence from chronic nicotine administration (Balfour 1990;Carroll et al 1989;Corrigall et al 1989;Hall and Morrison 1973;Shoaib and Bizarro 2004). Mecamylamine-precipitated withdrawal in nicotine-dependent rats has been reported with several other behavioral methods including observational tests (Malin et al 1994), conditioned place aversion tests (Suzuki et al 1996), and with locomotor activity (Malin et al 1994).…”

“…Several methods have been used to induce nicotine dependence in rats including intermittent injections through subcutaneous (Balfour 1990;Corrigall et al 1989), intracerebral (Hildebrand et al 1997), and intravenous routes (Carroll et al 1989), intradietary administration (Halladay et al 1999), as well as continuous drug infusion via osmotic minipumps (see review by Malin 2001;Shoaib and Bizarro 2004). This study demonstrated that osmotic minipumps infusing a range of nicotine doses (3, 6, and 12 mg/ kg per day) can induce behavioral dependence upon nicotine in rats.…”

“…In laboratory animals, dependence upon nicotine has been inferred by the emergence of withdrawal effects characterized by changes in conditioned behaviors (Balfour 1990;Carroll et al 1989;Corrigall et al 1989;Hall and Morrison 1973;Morrison 1974;Shoaib and Bizarro 2004), somatic signs including writhing, eye blinking, and gasping (see Malin 2001), and motivational or affective signs of withdrawal that are observed using brain stimulation reward threshold procedures (Watkins et al 2000a,b). Disruption of conditioned behaviors has been found to be particularly sensitive to the dependence-inducing effects of drugs which are not considered to regularly have marked somatic withdrawal effects such as with tetrahydrocannabinol (Beardsley et al 1984;Beardsley and Martin 2000) or the dissociative anesthetics (Beardsley and Balster 1987), or to low-dosage regimens of more classical dependenceproducing drugs such as the opiates (Gellert and Sparber 1977;Sparber and Meyer 1978).…”

Nicotinic systems and cognitive function

“…There is a rapid induction of hyperphagia, hyperdipsia and weight gain. Also, in contrast to the persisting effects described above, others (Morrison 1974a(Morrison , 1974bBalfour 1990) have found a marked reduction in shock avoidance after nicotine withdrawal. This may be related to the highly stressful nature of the tasks used.…”

The Role of NMDA Receptor Antagonists in Nicotine Tolerance, Sensitization, and Physical Dependence: A Preclinical Review

“…In the past, the evaluation of nicotine tolerance and withdrawal has been attempted using various models, including operant schedules of reinforcement,25,26,27 place preference,28 auditory startle,29 and activity,30 as well as discriminative stimulus effects of nicotine 31. However, the behavioral effects observed in these models in rodents appear to be complex and varied.…”