Address for correspondence: Dr. Frances M. Leslie, Department of Pharmacology, College of Medicine, University of California, Irvine, CA 92697-4625. Voice: 949-824-6699; fax: 949-824-4855. fmleslie{at}uci.edu
Although initiation of drug abuse occurs primarily during adolescence,
little is known about the central effects of nicotine and other
abused drugs during this developmental period. Here evidence,
derived from studies in rodents, is presented that suggests
that tobacco use initiation during early adolescence results
from a higher reward value of nicotine. The developmental profiles
of the rewarding effects of other abused drugs, such as cocaine,
differ from that of nicotine. Using
in situ hybridization to
quantify mRNA levels of the immediate early gene, cfos, the
neuronal activating effects of nicotine in limbic and sensory
cortices at different developmental stages are evaluated. Significant
age changes in basal levels of cfos mRNA expression in cortical
regions are observed, with a peak of responding of limbic cortices
during early adolescence. A changing pattern of nicotine-induced
neuronal activation is seen across the developmental spectrum,
with unique differences in both limbic and sensory cortex responding
during adolescence. An attentional set-shifting task was also
used to evaluate whether the observed differences during adolescence
reflect early functional immaturity of prefrontal cortices that
regulate motivated behavior and psychostimulant responding.
The finding of significantly better responding during adolescence
suggests apparent functional maturity of prefrontal circuits
and greater cognitive flexibility at younger ages. These findings
in rodent models suggest that adolescence is a period of altered
sensitivity to environmental stimuli, including abused drugs.
Further efforts are required to overcome technical challenges
in order to evaluate drug effects systematically in this age
group.
