Abstract:
Cigarette smoking is often associated with anxiety disorders. Evidence has
accumulated to indicate that smokers may be at a greater risk for the development of an
anxiety disorder. A neural basis has not been established for the transition between
smoking and anxiety-related behavior. To address this question, rats at postnatal day (P)
32 (adolescent) and P61 (adult) were administered subcutaneous injections of nicotine
(0.5 mg/kg; free base) or saline control three times per week (Mon., Wed., Fri.) for two
weeks (6 total injections). Seventeen days following nicotine cessation, rats were tested
for fear conditioning and fear extinction. Rats dosed with nicotine during adolescence
exhibited no alterations in later fear conditioning and fear extinction. In contrast, adult
nicotine exposure enhanced conditioned fear retrieval, but had no lasting effect on fear
extinction. Twenty-four hours following behavioral testing, brains were extracted for
Golgi-cox staining and dendrites of principal neurons from the basolateral amygdala
complex (BLA) and pyramidal neurons from the infralimbic cortex (IL) were digitally
reconstructed for morphometric analysis. In the adult group, enhanced fear retrieval was
accompanied by increased complexity of basilar dendrites in the BLA. In the adolescent
group, nicotine was found to reduce apical dendritic arbors. Dendritic remodeling was
lateralized in the BLA for both age groups. Dendrites were unaffected by nicotine in the
IL, indicating region-specific dendritic alteration in response to nicotine. Together, these
data implicate dendritic reorganization in the amygdala as a factor in development of
anxiety-related behavior following cessation from chronic nicotine exposure.
