Background: Caffeine / nicotine are some of the most abused stimulants in the world, even though they are extremely addictive and dangerous to the human health.  Maternal smoking during pregnancy has been reported as a strong risk factor for neurobehavioral alteration in offspring.  However, the neurophysiological changes and the cognitive related behavioral alterations in the offspring are not well elucidated. 

Methods: Hence, nicotine (6 mg/kg/day, mini-pump-infusion, PREN) was administered to pregnant dams and cognitive behavioral changes and neurophysiological alterations were elucidated. 

Results and Discussion: PREN-induced neurophysiological changes resulting in significant cognitive alteration as seen by spatial memory deficits in PREN using Y-maze test.  Furthermore, basal synaptic transmission and long-term potentiation (LTP) were decreased in the Schaffer collateral-CA1 synapses of PREN animals. Moreover, the amplitude and frequency of AMPAR-mediated spontaneous excitatory postsynaptic currents (sEPSCs) recorded from PREN hippocampal slices were significantly reduced. The deficits in LTP and basal synaptic transmission were accompanied by alterations in the function and expression of synaptic α7/β2 nicotinic acetylcholine receptors (nAChRs). In addition, co-immunoprecipitation studies in rat hippocampi revealed that α7/β2 nAChRs complex with vesicular glutamate transporter (VGLUT), postsynaptic density protein-95 (PSD-95) and synapse-associated protein (SAP102) were altered. Interestingly, the nicotinic receptor signaling CAMKII-ERK-CREB pathway is also altered in PREN. Taken together, our study suggests that alterations in nAChRs expression and function lead to modified glutamatergic transmission in the hippocampus resulting in memory deficits in PREN rodents.