Maternal smoking (MS) affects fetal development and

The Effects of Gestational Nicotine on the Stress Response in Adolescent Male and Female Rats
Anna J. Khalaj
Mentor: Frances Leslie
Clinical studies have shown that maternal smoking can cause persisting neurobehavioral deficits
in offspring, including Attention Deficit Hyperactivity Disorder, Conduct Disorder, and
increased substance abuse. These deficits manifest during childhood or adolescence and are
partly mediated by the dopamine (DA) system. Nicotine, the main psychoactive ingredient in
tobacco, acts on nicotinic acetylcholine receptors, which are found on DA neurons in the
developing brain. To investigate the effects of gestational nicotine (GN) on brain development,
we implanted pregnant dams with osmotic minipumps containing either nicotine (3mg/kg/day)
(GN) or saline (GS). During adolescence (postnatal day 32), female and male offspring were
injected with either cocaine (15mg/kg, i.p.) or saline, with or without a saline preinjection, and
were monitored for locomotor activity. Females had higher cocaine-induced activity than males,
but their behavior was sensitive to the stress of a prior saline injection. GS and GN females,
however, had opposite reactions to the preinjections: GS females showed a decrease in behavior,
while GN females showed an increase. To better understand this difference, we examined the
peripheral stress response by measuring plasma corticosterone. Although females showed
significantly higher levels than males, there was no significant difference between GS and GN
females. We are now analyzing the central stress response by measuring cfos activation, and
colocalization with corticotrophin releasing factor (CRF), in the paraventricular nucleus (PVN),
central amygdala (CeA), and bed nuclei of the stria terminalis (BNST). Preliminary analyses
show that cfos and CRF are colocalized in the PVN, but not the BNST or CeA.