Giuseppe Giannotti1, Lucia Caffino1, Francesca Mottarlini1, Giorgio Racagni1, Fabio Fumagalli2. 1. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milano, Italy. 2. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milano, Italy. Fabio.Fumagalli@unimi.it.
Abstract
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: 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.
Authors: S J Evans; P V Choudary; C R Neal; J Z Li; M P Vawter; H Tomita; J F Lopez; R C Thompson; F Meng; J D Stead; D M Walsh; R M Myers; W E Bunney; S J Watson; E G Jones; H Akil Journal: Proc Natl Acad Sci U S A Date: 2004-10-13 Impact factor: 11.205