Neural mechanisms underlying nicotine as a 'gateway' drug
Initial Award Abstract
Epidemiological studies have established that drug use is initiated in adolescence with tobacco and alcohol and progresses to marijuana and other illicit drugs. These findings have led to the hypothesis that alcohol and tobacco are ‘gateway’ drugs that sensitize central reward pathways to the effects of illicit drugs like cocaine. I have developed a unique animal model to test the ability of nicotine to act as a 'gateway' drug and examine the underlying neural mechanisms.
I have previously published findings that brief treatment with a low dose of nicotine greatly increases cocaine self-administration in adolescent animal model, but not in adults. In addition, this drug pretreatment effect did not generalize to all rewards, since nicotine did not increase responding for sucrose pellets in adolescents. Results from Specific Aim 1 show that this sensitization to cocaine’s reinforcing effects was accompanied by an increase in locomotor response to repeated, but not acute, cocaine injections in nicotine-pretreated adolescents. I also examined the neuroanatomical changes that result from this nicotine pretreatment using radioligand binding proposed in Specific Aim 2. Density of the serotonin transporter showed a significant interaction of age and pretreatment in the prefrontal cortex and basolateral amygdala, both regions that undergo maturation during the adolescent period. In addition, dopamine D3 receptor binding showed an interaction of age and pretreatment in the medial habenula. The results from the locomotor and radioligand binding experiments are currently being prepared for publication.
Over the next year, my goals are to continue the functional characterization of this nicotine pretreatment effect. My findings to date provide evidence that the adolescent brain is uniquely vulnerable to the effects of nicotine and support the ‘gateway’ hypothesis of teenage drug use. These studies should serve to clarify the underlying mechanisms of how tobacco may act as a ‘gateway’ drug in adolescence. |