BACKGROUND: Rats given extended access to cocaine develop several symptoms of addiction, including a gradual escalation of drug intake, whereas rats given limited access do not. We asked here whether extended access to cocaine also produces drug-induced sensitization, a form of neurobehavioral plasticity implicated in addiction. METHODS: Rats were given limited (1 hour/session) or extended access (6 hours/session) to self-administered cocaine. Following a period of abstinence, rats were selected at random for assessment of their psychomotor response to cocaine or drug-seeking during extinction or for anatomic studies. RESULTS: When re-exposed to cocaine, rats allowed extended drug access showed greater drug-seeking behavior and were hypersensitive (sensitized) to the psychomotor activating effects of cocaine compared with rats given limited access. Extended access to cocaine was also associated with a greater increase in the density of dendritic spines on neurons specifically in the core of the nucleus accumbens (and not in the shell or medial or orbital frontal cortex). CONCLUSIONS: The transition from stable to escalated cocaine use, a hallmark of addiction, is associated with especially robust behavioral sensitization and synaptic reorganization in the core of the nucleus accumbens.
BACKGROUND:Rats given extended access to cocaine develop several symptoms of addiction, including a gradual escalation of drug intake, whereas rats given limited access do not. We asked here whether extended access to cocaine also produces drug-induced sensitization, a form of neurobehavioral plasticity implicated in addiction. METHODS:Rats were given limited (1 hour/session) or extended access (6 hours/session) to self-administered cocaine. Following a period of abstinence, rats were selected at random for assessment of their psychomotor response to cocaine or drug-seeking during extinction or for anatomic studies. RESULTS: When re-exposed to cocaine, rats allowed extended drug access showed greater drug-seeking behavior and were hypersensitive (sensitized) to the psychomotor activating effects of cocaine compared with rats given limited access. Extended access to cocaine was also associated with a greater increase in the density of dendritic spines on neurons specifically in the core of the nucleus accumbens (and not in the shell or medial or orbital frontal cortex). CONCLUSIONS: The transition from stable to escalated cocaine use, a hallmark of addiction, is associated with especially robust behavioral sensitization and synaptic reorganization in the core of the nucleus accumbens.
Authors: Carrie R Ferrario; Jessica A Loweth; Mike Milovanovic; Kerstin A Ford; Gregorio L Galiñanes; Li-Jun Heng; Kuei Y Tseng; Marina E Wolf Journal: Neuropharmacology Date: 2011-01-27 Impact factor: 5.250
Authors: Teresa R Franklin; Ze Wang; Joshua Shin; Kanchana Jagannathan; Jesse J Suh; John A Detre; Charles P O'Brien; Anna Rose Childress Journal: Brain Struct Funct Date: 2013-01 Impact factor: 3.270
Authors: Dani Dumitriu; Quincey Laplant; Yael S Grossman; Caroline Dias; William G Janssen; Scott J Russo; John H Morrison; Eric J Nestler Journal: J Neurosci Date: 2012-05-16 Impact factor: 6.167
Authors: Florence R Theberge; Xuan Li; Sarita Kambhampati; Charles L Pickens; Robyn St Laurent; Jennifer M Bossert; Michael H Baumann; Mark R Hutchinson; Kenner C Rice; Linda R Watkins; Yavin Shaham Journal: Biol Psychiatry Date: 2013-02-04 Impact factor: 13.382
Authors: Allison R Bechard; Amber LaCrosse; Mark D Namba; Brooke Jackson; Lori A Knackstedt Journal: Drug Alcohol Depend Date: 2018-09-25 Impact factor: 4.492
Authors: Scott J Russo; Matthew B Wilkinson; Michelle S Mazei-Robison; David M Dietz; Ian Maze; Vaishnav Krishnan; William Renthal; Ami Graham; Shari G Birnbaum; Thomas A Green; Bruce Robison; Alan Lesselyong; Linda I Perrotti; Carlos A Bolaños; Arvind Kumar; Michael S Clark; John F Neumaier; Rachael L Neve; Asha L Bhakar; Philip A Barker; Eric J Nestler Journal: J Neurosci Date: 2009-03-18 Impact factor: 6.167