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The Journal of Neuroscience, March 5, 2008, 28(10):2375-2382; doi:10.1523/JNEUROSCI.5064-07.2008

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Behavioral/Systems/Cognitive
Transient D₁ Dopamine Receptor Expression on Prefrontal Cortex Projection Neurons: Relationship to Enhanced Motivational Salience of Drug Cues in Adolescence

Heather C. Brenhouse, Kai C. Sonntag, and Susan L. Andersen

McLean Hospital, Belmont, Massachusetts 02478

Correspondence should be addressed to Susan L. Andersen, McLean Hospital, 115 Mill Street, Belmont, MA 02478. Email: sandersen{at}mclean.harvard.edu

Adolescence is a transitional period during development that is associated with a greater likelihood of addiction to drugs than any other age. In the prefrontal cortex (PFC), D₁ dopamine receptors mediate motivational salience attribution, which plays a role in addiction. Here, we investigated the relationship of age-related D₁ dopamine receptor expression in the PFC with the maturation of cocaine place conditioning. Confocal microscopy revealed that retrogradely traced cortical output neurons to the nucleus accumbens express higher levels of D₁ receptors during adolescence compared with younger and older ages. D₁ expression does not change on GABAergic interneurons across age. Adolescent differences in D₁ expression occur independently of cortical-accumbens connectivity, which proliferates through adulthood. Behaviorally, adolescent rats are more sensitive to cocaine place conditioning than younger and older rats. However, microinjections of the D₁ antagonist SCH23390 into the PFC blocked adolescent place preferences, whereas microinjections of D₁ agonists dose-dependently increased preferences for cocaine-associated environments previously not preferred by juveniles. These results suggest that the heightened expression of D₁ receptors on cortical-accumbens projections may help explain increased sensitivity to environmental events and addictive behaviors during adolescence, whereas the paucity of D₁-expressing projections may reduce risk in juveniles.

Key words: adolescence; cocaine; place conditioning; retrograde tracer; D₁ dopamine; PFC

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Received Aug. 24, 2007; revised Jan. 17, 2008; accepted Jan. 17, 2008.

Correspondence should be addressed to Susan L. Andersen, McLean Hospital, 115 Mill Street, Belmont, MA 02478. Email: sandersen{at}mclean.harvard.edu

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