The role of dopamine in adolescent vulnerability to addiction
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1
The Florey Institute of Neuroscience and Mental Health, Behavioural Neuroscience Division, Australia
It is well-known that adolescence is a particularly vulnerable age for drug addiction. However, there is no animal model that explains why we are more vulnerable during adolescence. Hence the discovery of behavioral as well as pharmacological therapy has been greatly hindered. We have developed an animal model that explains adolescent vulnerability to cocaine and methamphetamine addiction. This model highlights that adolescents are more resistant to treatment and likely to relapse due to cue extinction deficits. Extinction forms the basis of exposure therapies that inhibit the salience of the cues and the environments associated with drug use. When P34 (adolescent) and P69 (adult) rats received extinction to a cocaine- or meth-associated cue following a period of intravenous self-administration, it proved effective in reducing cue-induced reinstatement in adults, but not in adolescents. A likely explanation for the differential extinction observed in adolescents relates to how dopaminergic signaling in the adolescent PFC is dominated by D1R compared to D2R. Indeed, when we increased D2R activity via intra-infralimbic cortex infusion of quinpirole, or via systemic injection of the selective D2 partial-agonist Aripiprazole prior to cue extinction in adolescent rats, cue-induced reinstatement was significantly reduced the next day. Interestingly, genome-wide transcriptome analyses revealed that meth self-administration during adolescence leads to a more dramatic neuroplasticity compared to self-administration during adulthood, that may lead to more extinction-resistant meth-related memories formed in adolescence. Our findings suggest a new direction in addiction therapeutics, especially during adolescence.
Keywords:
Dopamine,
Gene Expression,
Prefrontal Cortex,
neuroplasticity,
drug addiction
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
Symposium 9: Neurochemical Mechanisms Underlying Vulnerability to Drug Addiction
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
Kim
J
(2016). The role of dopamine in adolescent vulnerability to addiction.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00038
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Received:
26 Jul 2016;
Published Online:
11 Aug 2016.
*
Correspondence:
Dr. Jee Hyun Kim, The Florey Institute of Neuroscience and Mental Health, Behavioural Neuroscience Division, Parkville, VIC, Australia, drjeehyunkim@gmail.com