Unraveling Withdrawal: The Role of Orexin A in Attentional Deficits Following Nicotine Withdrawal

Nicotine is a psychostimulant that is known for its highly addictive nature and affects many brain pathways involved in attention, learning, and memory. Nicotine withdrawal is known to disrupt these cognitive processes. Orexins are excitatory neuropeptides found in the brain and are expressed in areas that focus on attention and motivation among other functions. Previous literature suggests orexin levels decline during nicotine withdrawal, which may contribute to the cognitive decline experienced during withdrawal. The present study is designed to test whether orexin A administration can reduce attention-based deficits experienced during nicotine withdrawal. The study included two phases. After training in a visual sustained attention task, experimental animals (n=9) were injected with nicotine (0.1 mg/kg) twice per day for five days. After this time period, nicotine was stopped and rats were given a randomized selection of intranasal infusions of saline or orexin A (100uM) prior to attention task performance. We hypothesized that nicotine would improve attentional accuracy and that orexin A would improve the negative attentional-based deficits from nicotine withdrawal. The present data suggests that repeated nicotine administration improves signal detection accuracy in an attention-demanding task. Nicotine administration had no effect on trials when no signal was presented and no effect on the rate of responding. When nicotine administration ceased, hit accuracy significantly diminished demonstrating attentional decline during nicotine withdrawal. The orexin-A treatment didn’t significantly improve accuracy impairments seen from withdrawal but it did significantly reduce average omissions. Through this research we can establish a relationship between nicotine and attention as well as the possibility of orexins as a treatment for the attentional or motivational deficits experienced during nicotine withdrawal.