title: The antimetabolite ara-CTP blocks long-term memory of conditioned taste aversion.
abstract: We examined the hypothesis that processes related to DNA recombination and repair are involved in learning and memory. Rats received intracerebroventricular (i.c.v.) infusions of the antimetabolite 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP) or its precursor cytosine arabinoside (ara-C) 30 min prior to conditioned taste aversion (CTA) training. Both ara-CTP and ara-C caused significant impairments in long-term memory (LTM) of CTA. Control experiments indicate that the effect of ara-CTP on CTA memory is related to interference with learning. Furthermore, as it was previously demonstrated for the protein synthesis inhibitor anisomycin, ara-CTP had no effect on CTA memory when it was injected 1 h after training. Importantly, although both ara-CTP and anisomycin significantly blocked LTM in the task, short-term memory (STM) measured 1 h after training was not affected by either of the drugs. Finally, ara-CTP had no effect on in vitro transcription, but it did effectively block nonhomologous DNA end joining (NHEJ) activity of brain protein extracts. We suggest that DNA ligase-mediated DNA recombination and repair processes are necessary for the expression of LTM in the brain.
authors.affiliation: Department of Biology, University of Puerto Rico, San Juan 00931-3360, Puerto Rico, USA.
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Wang
authors.forename: Keqin
authors.initials: K
authors.lastname: Ren
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez
authors.forename: Alcino J
authors.initials: AJ
authors.lastname: Silva
authors.forename: Sandra
authors.initials: S
authors.lastname: Peña de Ortiz
mesh_terms: D000818:Animals; D001085:Arabinofuranosylcytosine Triphosphate / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects*; D003561:Cytarabine / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D011995:Recombination, Genetic; D013649:Taste; D014158:Transcription, Genetic
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate