title: Short- and long-term anxiogenic effects induced by a single injection of subconvulsant doses of pilocarpine in rats: investigation of the putative role of hippocampal pathways.
abstract: BACKGROUND
  Behavioral consequences of convulsive episodes are well documented, but less attention was paid to changes that occur in response to subconvulsant doses of drugs.
  
  
  OBJECTIVE
  We investigated short- and long-term effects of a single systemic injection of a subconvulsant dose of pilocarpine on the behavior of rats as evaluated in the elevated plus maze.
  
  
  RESULTS
  Pilocarpine induced an anxiogenic-like profile 24 h later, and this effect persisted for up to 3 months (% of time spent on open arms at 24 h, control = 35.47 ± 3.23; pilocarpine 150 = 8.2 ± 2.6; 3 months, control = 31.9 ± 5.5; pilocarpine 150 = 9.3 ± 4.9). Temporary inactivation of fimbria-fornix with lidocaine 4% promoted an anxiolytic-like effect per se, suggesting a tonic control of this pathway on the modulation of anxiety-related behaviors. Lidocaine also reduced the anxiogenic-like profile of animals tested 1 month after pilocarpine treatment (% of time spent on open arms, saline + phosphate-buffered saline (PBS) = 31.7 + 3.7; saline + lidocaine = 54.4 + 4.7; pilocarpine + PBS = 10.3 + 4.1; pilocarpine + lidocaine = 40.1 + 9.1). To determine whether the anxiogenic-like effect was mediated by septal region or by direct hippocampal projections to the diencephalon, the neural transmission of post-commissural fornix was blocked, and a similar reduction in the anxiogenic-like effect of pilocarpine was observed.
  
  
  CONCLUSIONS
  Our findings suggest that a single systemic injection of pilocarpine may induce long-lasting anxiogenic-like behavior in rats, an effect that appears to be mediated, in part, through a direct path from hippocampus to medial hypothalamic sites involved in fear responses.
authors.affiliation: Department of Pharmacology, CCB, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil.
authors.forename: Filipe Silveira
authors.initials: FS
authors.lastname: Duarte
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Gavioli
authors.forename: Marcelo
authors.initials: M
authors.lastname: Duzzioni
authors.forename: Alexandre Ademar
authors.initials: AA
authors.lastname: Hoeller
authors.forename: Newton Sabino
authors.initials: NS
authors.lastname: Canteras
authors.forename: Thereza Christina Monteiro
authors.initials: TC
authors.lastname: De Lima
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D020712:Fornix, Brain / Q000187:drug effects / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008012:Lidocaine / Q000008:administration & dosage; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000633:toxicity*; D009434:Neural Pathways / Q000187:drug effects* / Q000503:physiopathology; D010862:Pilocarpine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D018721:Muscarinic Agonists; D010862:Pilocarpine; D008012:Lidocaine
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