Search

Rationale and Objectives: Among the changes caused by repeated exposure to drugs of abuse, structural rearrangements play a critical role, setting the stage for maladaptive responses to environmental challenges and sustaining drug-taking and drug-seeking behaviors. Given that adolescents are more vulnerable to drug abuse than adults and based on our recent data showing that a single exposure to cocaine during adolescence is sufficient to change the adolescent brain, we decided to investigate whether acute cocaine exposure may alter actin remodeling in reward-related brain regions., Methods: Accordingly, we decided to evaluate if F-actin/G-actin ratio was altered by a single injection of cocaine (20 mg/kg) at postnatal day 35. We also evaluated whether the first administration of cocaine influences such a ratio in response to a second injection (10 mg/kg) provided 24 h or 7 days later., Results: Within the medial prefrontal cortex, a single cocaine injection increases the F-actin/G-actin ratio. This effect lasts 1 week, and it is not affected by the second injection of cocaine, indicating a persistent effect of the first exposure. In the nucleus accumbens, cocaine reduces the F-actin/G-actin ratio 24 h later. Seven days later, instead, such a ratio is markedly increased: notably, the additional exposure to the psychostimulant normalizes the F-actin/G-actin ratio., Conclusions: These results suggest that a single cocaine injection during adolescence causes possible changes in actin dynamics and influences the response to a second challenge of the psychostimulant, indicating that early cocaine priming might affect mechanisms regulating synaptic structural plasticity in specific brain regions.

Rationale: Adolescence is a period of high vulnerability to drugs of abuse and alterations of the proper developmental trajectory via psychostimulant exposure might change the physiological brain homeostasis., Objective: By microdissection of brain areas via punching, we investigated whether repeated exposure to cocaine during adolescence (from postnatal day 28 [PND28] to PND42) has altered fibroblast growth factor-2 (FGF-2) messenger RNA (mRNA) levels in selected brain subregions critical for the action of cocaine., Results: We found a reduction of FGF-2 mRNA levels in ventral tegmental area (VTA), where mesocortical and mesolimbic pathways originate. The analysis of the trophic factor levels in the distal projecting regions revealed a selective reduction of FGF-2 mRNA levels in infralimbic (IL) subregion of the medial prefrontal cortex (the terminal region of the mesocortical pathway) and in the nucleus accumbens core (cNAc) (the terminal region of the mesolimbic pathway). Last, we found reduced FGF-2 mRNA levels also in brain regions which, although in a different manner, contribute to the reward system, i.e., the central nucleus of amygdala (cAmy) and the ventral portion of hippocampus (vHip)., Conclusion: The widespread and coordinated reduction of FGF-2 mRNA levels across the brain's reward neurocircuitry might represent a defensive strategy set in motion to oppose to the psychostimulant properties of cocaine. Moreover, given the role of FGF-2 in modulating mood disorders, the reduced trophic support here observed might sustain the negative emotional state set in motion by repeated exposure to cocaine.

Rationale: During adolescence, the brain is maturing and more sensitive to drugs of abuse that can influence its developmental trajectory. Recently, attention has been focused on basic fibroblast growth factor (FGF-2) given that its administration early in life enhances the acquisition of cocaine self-administration and sensitization at adulthood (Turner et al. (Pharmacol Biochem Behav 92:100-4, 2009), Clinton et al. (Pharmacol Biochem Behav103:6-17, 2012)). Additionally, we found that abstinence from adolescent cocaine exposure long lastingly dysregulates FGF-2 transcription (Giannotti et al. (Psychopharmacology (Berl) 225:553-60, 2013 )., Objectives: The objectives of the study are to evaluate if (1) a single injection of cocaine (20 mg/kg) at postnatal day 35 alters FGF-2 messenger RNA (mRNA) levels and (2) the first injection influences the trophic response to a second injection (10 mg/kg) provided 24 h or 7 days later., Results: We found regional differences in the FGF-2 expression pattern as either the first or the second injection of cocaine by themselves upregulated FGF-2 mRNA in the medial prefrontal cortex and nucleus accumbens while downregulating it in the hippocampus. The first injection influences the trophic response of the second. Of note, 24 h after the first injection, accumbal and hippocampal FGF-2 changes produced by cocaine in saline-pretreated rats were prevented in cocaine-pretreated rats. Conversely, in the medial prefrontal cortex and hippocampus 7 days after the first injection, the cocaine-induced FGF-2 changes were modified by the subsequent exposure to the psychostimulant., Conclusions: These findings show that a single cocaine injection is sufficient to produce enduring changes in the adolescent brain and indicate that early cocaine priming alters the mechanisms regulating the trophic response in a brain region-specific fashion.