Inhibitory learning is modulated by nicotinic acetylcholine receptors

Abstract

Prior research has established that stimulating nicotinic acetylcholine receptors can facilitate learning and memory. However, most studies have focused on learning to emit a particular behavior, while little is known about the effects of nicotine on learning to withhold a behavioral response. The present study consisted of a dose response analysis of the effects of nicotine on negative occasion setting, a form of learned inhibition. In this paradigm, rats received one type of training trial in which presentation of a tone by itself was followed immediately by food reward. During the other type of trials, the tone was preceded by presentation of a light and no food was delivered after the tone. Rats gradually learned to approach the cup in anticipation of receiving food reward during presentations of the tone alone, but withheld that behavior when the tone was preceded by the light. Nicotine (0.35mg/kg) facilitated negative occasion setting by reducing the number of sessions needed to learn the discrimination between trial types and by reducing the rate of responding on non-reinforced trials. Nicotine also increased the orienting response to the light, suggesting that nicotine may have affected the ability to withhold food cup behavior on non-reinforced trials by increasing attention to the light. In contrast to the effects of nicotine, rats treated with mecamylamine (0.125, 0.5, or 2 mg/kg) needed more training sessions to discriminate between reinforced and non-reinforced trials compared to saline-treated rats. The findings indicate that nicotinic acetylcholine receptors may be active during negative occasion setting and that nicotine can potentiate learned inhibition.

Nicotine administration enhances negative occasion setting in adolescent rats

“…Finally, these data are consistent with previous findings from our laboratory indicating that administration of nicotine enhances negative occasion setting in adult rats [10], suggesting that the effects in adolescents may be mediated by similar neurobiological mechanisms. However, although cholinergic innervation of regions that are necessary for negative occasion setting (e.g., prefrontal cortex) are present by adolescence [24], more recent behavioral evidence suggests the functional capacity of this system remains underdeveloped for much longer [25].…”

“…Behavioral training subsequently began on post-natal day (PND) 35 and continued for 20 days. Vehicle solution or (−) nicotine hydrogen tartrate (equivalent of 0.35 mg/kg free-base nicotine, Sigma Aldrich Co., St. Louis, MO, USA) was prepared daily and administered 10 min before each training session [10]. The behavioral procedures were carried out in standard conditioning chambers as described previously [9].…”

“…The difference in responding during the tone on the two trial types was calculated and Z-scores were generated by dividing the difference by the SEM of the difference in responding. Successful discrimination between the two trial types was defined as a greater amount of time spent in the food cup during presentation of the tone on reinforced trials than during non-reinforced trials (a Z-score of at least 2.325, P < 0.01) for 3 consecutive daily sessions, as in prior studies [9, 10]. In addition, the difference in responding between trial types was subjected to a repeated-measures analysis of variance (ANOVA).…”

“…Orienting was defined as rearing on the hind legs with both forepaws off the ground and was assessed by measuring the amount of time that photobeams mounted just under the light stimulus were broken. Orienting behavior is an often-used measure of attentional processing of a stimulus [11] and previous work has shown that nicotine may enhance inhibition of responding to the target stimulus on non-reinforced trials by increasing attention to the feature stimulus [10]. As shown in Figure 3, nicotine-treated rats exhibited significantly higher levels of rearing behavior [ t (14) = −5.6, p < 0.001] during presentation of the light compared to vehicle-treated.…”

Negative occasion setting in juvenile rats

“…Z-scores were calculated by dividing that result by the SEM of the difference in responding across all rats in a group. Successful discrimination between the two trial types was defined as a greater amount of time spent in the food cup during presentation of the tone on reinforced trials than during non-reinforced trials (a Z-score of at least 2.325, P < 0.01) for 3 consecutive daily sessions, as in prior studies [12, 32]. …”