Long-Lasting Cognitive Deficits Resulting from Adolescent Nicotine Exposure in Rats

Abstract

Adolescence is a developmental period, during which the brain and particularly medial prefrontal cortical (mPFC) regions thereof have not fully matured. Because epidemiological data have suggested that adolescent nicotine use may result in disturbances in cognitive function in adulthood, we investigated the long-term effects of adolescent nicotine exposure in rats. Male Wistar rats were exposed to either nicotine (three times daily, 0.4 mg/kg s.c.) or saline for 10 days during (postnatal day (PND) 34-43) or following (PND 60-69) adolescence. After 5 weeks during adulthood, separate groups of animals were tested in operant paradigms taxing attention and distinct measures of impulsivity. Visuospatial attention and impulsive action were tested in the five-choice serial reaction time task, whereas impulsive choice was assessed in the delayed reward task. Our data show that adolescent, but not postadolescent, nicotine exposure affects cognitive performance in adulthood and results in diminished attentional performance and increments in impulsive action, while leaving impulsive choice intact. This altered cognitive performance appeared to be associated with enhanced releasability of dopamine in the mPFC. Together, these data suggest that adolescence is a time window during which the brain is vulnerable to long-lasting cognitive disturbances resulting from nicotine exposure.

Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence

“…Similar to findings from human epidemiological data, adolescent nicotine exposure in rats has long-term effects on attentional processing 9 . The 5-choice serial reaction time task (5-CSRTT) is the most widely employed translational paradigm that has tremendously contributed to our understanding of the neural correlates of divided and sustained attention and impulsive action 10,11 .…”

Nicotinic actions on neuronal networks for cognition: General principles and long-term consequences

“…Animals that received nicotine during adolescence showed a doubling in premature responses and a reduction in correct responses, suggesting increased impulsive behaviour and reduced attention performance [134]. Animals that received nicotine as adults did not show changes in impulsivity nor in attention performance [134]. What the mechanisms are underlying these lasting effects of nicotine on cognitive performance is at this point unknown.…”

“…Rats were trained in the 5 choice serial reaction time task [44] and were injected with either nicotine or saline for 10 days during adolescence (postnatal days 34 -43) and attention performance was tested 5 weeks after the animals received the last injection with nicotine. Animals that received nicotine during adolescence showed a doubling in premature responses and a reduction in correct responses, suggesting increased impulsive behaviour and reduced attention performance [134]. Animals that received nicotine as adults did not show changes in impulsivity nor in attention performance [134].…”

“…The key question now is of course, does adolescent nicotine exposure result in lasting altered cognitive function? Recently, this question was addressed by Counotte et al [134]. Rats were trained in the 5 choice serial reaction time task [44] and were injected with either nicotine or saline for 10 days during adolescence (postnatal days 34 -43) and attention performance was tested 5 weeks after the animals received the last injection with nicotine.…”

Neural Correlates of Response Inhibition and Cigarette Smoking in Late Adolescence

“…In rodents, frontostriatal circuitry is especially susceptible to nicotine exposure during adolescence (Schochet et al, 2005), with subsequent cognitive deficits in adulthood (Counett et al, 2009;Fountain et al, 2008). It has been proposed that neurotoxic effects during adolescence, when neural circuitry that subserves inhibitory control undergoes significant development, explain why early initiation of cigarette smoking leads to higher levels of nicotine dependence (Mathers et al, 2006).…”