Lucia Caffino1, Giuseppe Giannotti1, Giorgio Racagni1, Fabio Fumagalli2. 1. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. 2. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. Fabio.Fumagalli@unimi.it.
Abstract
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 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.
Authors: Lucia Caffino; Francesca Calabrese; Giuseppe Giannotti; Alessandro Barbon; Michel M M Verheij; Giorgio Racagni; Fabio Fumagalli Journal: Addict Biol Date: 2013-09-16 Impact factor: 4.280
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Authors: Sarah E Dowd; Martina L Mustroph; Elena V Romanova; Bruce R Southey; Heinrich Pinardo; Justin S Rhodes; Jonathan V Sweedler Journal: ACS Omega Date: 2018-10-24