title: Working memory deficits and alterations of ERK and CREB phosphorylation following withdrawal from cocaine self-administration.
abstract: BACKGROUND
  The mechanisms underlying memory functions during withdrawal from the chronic drug use are poorly understood.
  
  
  METHODS
  We assessed learning and spatial working memory using the delayed alternation assay (T-maze) in rats, previously subjected to cocaine self-administration. The T-maze training was conducted 1-5 weeks after cocaine cessation; working memory efficacy was assessed at 5-8 weeks of drug withdrawal. After behavioral training and testing, the rats were sacrificed and the levels of p-CREB/CREB and p-ERK2/ERK2 in several brain areas were measured. The same molecular assessment was performed in rats with cocaine injections, but forced to drug abstinence in home cages.
  
  
  RESULTS
  After 5 weeks of cocaine withdrawal from self-administration, a significant impairment of working memory under increased working memory load (inter-trial delay extended to 30s), with no changes at baseline conditions (inter-trial delay 10s), was noticed. Neither acquisition phase nor working memory performance measured 6-8 weeks after the last drug intake differed between cocaine or saline pretreated rats. Upon T-maze training and 8-week withdrawal, cocaine-pretreated rats had higher levels of p-CREB/CREB in prefrontal cortex and dorsal striatum and lower in hippocampus compared to saline rats. Increased levels of p-ERK2/ERK2 were observed in dorsal striatum, hippocampus and decreased in nucleus accumbens. In cocaine-pretreated caged rats no changes in p-CREB/CREB levels were observed, while ERK2 levels either decreased (frontal cortex) or increased (nucleus accumbens).
  
  
  CONCLUSIONS
  Our results suggest that cocaine self-administration results in cognitive impairments and alterations in ERK/CREB signaling pathway long after discontinuation of drug use.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland; Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Fijał
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Nowak
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Leśkiewicz
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland; Department of Biochemical Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland; Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland. Electronic address: mal.fil@if-pan.krakow.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000523:psychology*; D008570:Memory, Short-Term / Q000187:drug effects*; D010766:Phosphorylation; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000523:psychology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein
keywords: Cocaine self-administration; Cocaine withdrawal; Delayed alternation task; Working memory