Prefrontal Dopaminergic Mechanisms of Extinction in Adolescence Compared to Adulthood in Rats
نویسندگان
چکیده
Adolescents with anxiety disorders attain poorer outcomes following extinction-based treatment compared to adults. Extinction deficit during adolescence has been identified to involve immaturity in the medial prefrontal cortex (mPFC). Findings from adult rodents suggest extinction involves dopamine signaling in the mPFC. This system changes dramatically during adolescence, but its role in adolescent extinction is unknown. Therefore, we investigated the role of prefrontal dopamine in extinction using Pavlovian fear conditioning in adolescent and adult rats. Using quantitative PCR (qPCR) analyses, we measured changes in dopamine receptor gene expression in the mPFC before and after extinction. We then enhanced dopamine 1 receptor (D1R) or dopamine 2 receptor (D2R) signaling in the infralimbic cortex (IL) of the mPFC using agonists at the time of extinction. Adolescent rats displayed a deficit in extinction retention compared to adults. Extinction induced a reduction in D1R compared to D2R gene expression in adolescent rats, whereas an increase of D1R compared to D2R gene expression was observed in adult rats. Acutely enhancing IL D1R signaling using SKF-81297 had no effect on extinction at either age. In contrast, acutely enhancing IL D2R signaling with quinpirole significantly enhanced long-term extinction in adolescents, and impaired within-session extinction in adults. Our results suggest a dissociated role for prefrontal dopamine in fear extinction during adolescence compared to adulthood. Findings highlight the dopamine system as a potential pharmacological target to improve extinction-based treatments for adolescents.
منابع مشابه
Forming competing fear learning and extinction memories in adolescence makes fear difficult to inhibit.
Fear inhibition is markedly impaired in adolescent rodents and humans. The present experiments investigated whether this impairment is critically determined by the animal's age at the time of fear learning or their age at fear extinction. Male rats (n = 170) were tested for extinction retention after conditioning and extinction at different ages. We examined neural correlates of impaired extinc...
متن کاملAripiprazole Facilitates Extinction of Conditioned Fear in Adolescent Rats
Anxiety disorders are the most common type of mental disorder during adolescence, which is at least partly due to the resistance to extinction exhibited at this age. The dopaminergic system is known to be dysregulated during adolescence; therefore, we aimed to facilitate extinction in adolescent rats using the dopamine receptor 2 partial agonist aripiprazole (Abilify™), and examine the behavior...
متن کاملThe Study of Apomorphine Effects and Heterogeneity in the Medial Prefrontal Cortex on the Dopaminergic Behaviors of Rats
Objective(s) While the nucleus accumbens and the striatum have received much attention regarding their roles in stereotyped behaviors, the role of the medial prefrontal cortex (mPFC) has not been investigated to the same degree. Few studies have reported the role of the mPFC in dopaminergic induction of locomotor hyperactivity. The mPFC is a heterogeneous area (the anterior cingulated, prelimbi...
متن کاملImmunohistochemical analyses of long-term extinction of conditioned fear in adolescent rats.
Adolescence is a period of heightened emotional reactivity and vulnerability to poor outcomes (e.g., suicide, anxiety, and depression). Recent human and animal neuroimaging studies suggest that dramatic changes in prefrontal cortical areas during adolescence are involved in these effects. The present study explored the functional implications of prefrontal cortical changes during adolescence by...
متن کاملEffects of chronic stress in adolescence on learned fear, anxiety, and synaptic transmission in the rat prelimbic cortex.
The prelimbic cortex and amygdala regulate the extinction of conditioned fear and anxiety, respectively. In adult rats, chronic stress affects the dendritic morphology of these brain areas, slowing extinction of learned fear and enhancing anxiety. The aim of this study was to determine whether rats subjected to chronic stress in adolescence show changes in learned fear, anxiety, and synaptic tr...
متن کامل