The antimetabolite ara-CTP blocks long-term memory of conditioned taste aversion.
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.
Wang
Jianpeng
J
Department of Biology, University of Puerto Rico, San Juan 00931-3360, Puerto Rico, USA.
Ren
Keqin
K
Pérez
Javier
J
Silva
Alcino J
AJ
Peña de Ortiz
Sandra
S
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
D019384:Nucleic Acid Synthesis Inhibitors; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate