title: Chronic cyclosporine-A injection in rats with damaged blood-brain barrier does not impair retention of passive avoidance.
abstract: Recently, we demonstrated that chronic administration of immunosuppressant drug, cyclosporine-A (CsA), does not produce impairment in memory retention of a passive avoidance task in normal adult rats. Since CsA has been used as an adjunctive therapy to avoid xenograft rejection inherent in neural transplantation therapy for neurodegenerative disorders, we replicated our previous study in animals with damaged blood-brain barrier (BBB) simulating that of the neural transplantation protocol. Adult rats with damaged BBB that received either chronic CsA (5, 10, and 20 mg/kg) or vehicle injection did not differ significantly in their memory retention of the passive avoidance task that rewarded 'less mobile activity', in that animals avoided electric shock when they restrained their movements within the safe compartment. General spontaneous locomotor activity also was not altered by CsA, except in animals that received 20 mg/kg, which displayed significant hypoactivity at later post-injection periods of CsA. The absence of potentiation of retention of the passive avoidance task in all CsA-treated animals, including the hypoactive ones, suggests that locomotor activity did not interfere with cognitive behavior. The present results confirm our previous findings that the therapeutic dosage (10 mg/kg) of CsA used for neural transplantation does not produce visible deleterious effects on the performance of memory retention task in immunosuppressed rats with damaged BBB.
authors.affiliation: Department of Cellular Neurophysiology, Intramural Research Program, National Institutes of Health, National Institute on Drug Abuse, Baltimore, MD 21224, USA. cborlong@intra.nida.nih.gov
authors.forename: C V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: T
authors.initials: T
authors.lastname: Fujisaki
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D012965:Sodium Chloride; D016572:Cyclosporine