Rationale While clinical studies show maternal consumption of palatable fat-rich diets during pregnancy to negatively impact the children’s behaviors and increase their vulnerability to drug abuse, the precise behavioral and neurochemical mechanisms mediating these phenomena have yet to be examined. Objective The study examined in rats whether gestational exposure to a high-fat diet (HFD) can increase the offspring’s propensity to use nicotine and whether disturbances in central nicotinic cholinergic signaling accompany this behavioral effect. Methods Rat offspring exposed perinatally to a HFD or Chow diet were characterized in terms of their nicotine self-administration behavior in a series of operant response experiments and the activity of acetylcholinesterase (AChE) and density of nicotinic ACh receptors (nAChRs) in different brain areas. Result Perinatal HFD compared to Chow exposure increased nicotine-self administration behavior during fixed-ratio and dose-response testing and caused an increase in breakpoint using progressive ratio testing, while nicotine-seeking in response to nicotine prime-induced reinstatement was reduced. This behavioral change induced by the HFD was associated with a significant reduction in activity of AChE in the midbrain, hypothalamus and striatum and increased density of β2-nAChRs in the ventral tegmental area and substantia nigra and of α7-nAChRs in the lateral and ventromedial hypothalamus. Conclusions Perinatal exposure to a HFD increases the vulnerability of the offspring to excessive nicotine use by enhancing its reward potential, and these behavioral changes are accompanied by a stimulation of nicotinic cholinergic signaling in mesostriatal and hypothalamic brain areas important for reinforcement and consummatory behavior.

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Background: The “drip and ship” protocol is an important treatment for acute ischemic stroke patients who do not have immediate access to comprehensive stroke centers (CSC). Intravenous thrombolysis is initiated at a primary stroke center followed by expeditious transfer to a CSC typically during the tPA infusion. National guidelines recommend attention to blood pressure control (<180/105 mmHg) during and after tPA administration for the first 24 hours. We sought to determine the frequency of BP protocol violations during transfer and the impact on patient outcomes. Methods: This is a retrospective analysis of 130 consecutive “drip and ship” patients transferred to North Shore University Hospital between July 2012 to June 2014. BP upon arrival to CSC was used to determine adherence to BP guidelines. Poor patient outcome was defined as discharge to hospice or expired, discharge modified Rankin score (mRS) >2, and symptomatic intracerebral hemorrhage (sICH). Results: A total of 123 patients were confirmed to have an ischemic stroke (7 stroke mimics were excluded). Blood pressure was available for 120 patients. Mean age of the cohort was 62.7 years (range 24 to 100 years). Mean CSC admission NIHSS was 11.0 (range 0 to 28). Mean BP upon CSC arrival was 143.3/77.8 (systolic range 90 to 200 mmHg/diastolic range 44 to 112 mmHg). Mean mRS at discharge was 2.76. Blood pressure parameter violations were documented in 15 (12.5%) patients. Of these, 7 (46.7%) were discharged to hospice or expired, whereas 9/105 (8.6%) without blood pressure parameter violation were discharged to hospice or expired. This difference was statistically significant (p<0.0006, Fisher’s exact test). Symptomatic ICH was observed in 1/15 (6.7%) patients with BP parameter violations and 10/105 (9.5%) patients without BP parameter violations (not significant). Eleven (73.3%) of 15 patients with BP violations had a discharge mRS >2, compared to 54/103 (52.4%) patients without BP parameter violation (not significant). Conclusions: Post thrombolysis blood pressure guideline violations during drip and ship transfer were significantly associated with in hospital mortality or discharge to hospice, but not with high discharge mRS or symptomatic ICH. Larger studies are needed to confirm these results.