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.
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.
Duarte
Filipe Silveira
FS
Department of Pharmacology, CCB, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil.
Gavioli
Elaine Cristina
EC
Duzzioni
Marcelo
M
Hoeller
Alexandre Ademar
AA
Canteras
Newton Sabino
NS
De Lima
Thereza Christina Monteiro
TC
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
D000779:Anesthetics, Local; D018721:Muscarinic Agonists; D010862:Pilocarpine; D008012:Lidocaine
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