Transgenerational effects of adolescent nicotine exposure in rats: Evidence for cognitive deficits in adult female offspring

Abstract

This study investigated whether adolescent nicotine exposure in one generation of rats would impair the cognitive capacity of a subsequent generation. Male and female rats in the parental F0 generation were given twice-daily i.p. injections of either 1.0 mg/kg nicotine or an equivalent volume of saline for 35 days during adolescence on postnatal days 25-59 (P25-59). After reaching adulthood, male and female nicotine-exposed rats were paired for breeding as were male and female saline control rats. Only female offspring were used in this experiment. Half of the offspring of F0 nicotine-exposed breeders and half of the offspring of F0 saline control rats received twice-daily i.p. injections of 1.0 mg/kg nicotine during adolescence on P25-59. The remainder of the rats received twice-daily saline injections for the same period. To evaluate transgenerational effects of nicotine exposure on complex cognitive learning abilities, F1 generation rats were trained to perform a highly structured serial pattern in a serial multiple choice (SMC) task. Beginning on P95, rats in the F1 generation were given either 4 days of massed training (20 patterns/day) followed by spaced training (10 patterns/day) or only spaced training. Transgenerational effects of adolescent nicotine exposure were observed as greater difficulty in learning a “violation element” of the pattern, which indicated that rats were impaired in the ability to encode and remember multiple sequential elements as compound or configural cues. The results indicated that for rats that received massed training, F1 generation rats with adolescent nicotine exposure whose F0 generation parents also experienced adolescent nicotine exposure showed poorer learning of the violation element than rats that experienced adolescent nicotine exposure only in the F1 generation. Thus, adolescent nicotine exposure in one generation of rats produced a cognitive impairment in the next generation.

Simplicity From Complexity in Vertebrate Behavior: Macphail (1987) Revisited

“…Furthermore, the learning and memory systems involved depend on different behavioral and neural systems as shown by dissociations observed in adulthood long after chronic adolescent drug exposure (Pickens et al, 2013;Renaud et al, 2015;Rowan et al, 2015;Renaud and Fountain, 2016;Sharp et al, 2019). Similar dissociations of cognitive behavioral systems can be seen in normal rats administered acute muscarinic cholinergic blockade (Pickens et al, 2013;Renaud et al, 2015;Rowan et al, 2015;Renaud and Fountain, 2016;Sharp et al, 2019).…”

“…Furthermore, the learning and memory systems involved depend on different behavioral and neural systems as shown by dissociations observed in adulthood long after chronic adolescent drug exposure (Pickens et al, 2013;Renaud et al, 2015;Rowan et al, 2015;Renaud and Fountain, 2016;Sharp et al, 2019). Similar dissociations of cognitive behavioral systems can be seen in normal rats administered acute muscarinic cholinergic blockade (Pickens et al, 2013;Renaud et al, 2015;Rowan et al, 2015;Renaud and Fountain, 2016;Sharp et al, 2019). The SMC method in mice and rats produces data comparable to data in humans in an analogous task (Fountain and Rowan, 1995) and rats use multiple cognitive processes concurrently: rule-learning, stimulus-response (S-R) learning, discrimination learning, and multiple-item memory Fountain, 2010, 2016).…”

Preclinical Models of Attention Deficit Hyperactivity Disorder: Neurobiology, Drug Discovery, and Beyond

“…demonstrating that the dopamine neurotransmitter mechanisms impacted by the prenatal nicotine exposure were transmitted transgenerationally as well (Zhu et al, 2014). Since then, a number of studies in human subjects (Golding et al, 2017(Golding et al, , 2020 as well as animal models (Buck et al, 2019;Liu et al, 2020;Renaud & Fountain, 2016;Yohn et al, 2015) have shown transgenerational transmission of traits following in utero nicotine exposure.…”

Adolescent Substance Abuse, Transgenerational Consequences and Epigenetics

“…measured using a serial multiple-choice task [ 52 ]. Currently, the mechanism(s) underlying the cross-generational consequences of nicotine exposure in adolescence are not well understood but suggest epigenetic modifications of the genome and future work should focus on the cellular events underlying the development of these phenotypic traits.…”