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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

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Abstract

Rationale

Behavioral consequences of convulsive episodes are well documented, but less attention was paid to changes that occur in response to subconvulsant doses of drugs.

Objectives

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.

Methods and 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.

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Acknowledgments

F. S. Duarte was a recipient of a post-doctoral fellowship from the Brazilian National Research Council (CNPq). A.A. Hoeller and M. Duzzioni are recipients of PhD fellowship from CAPES and CNPq, respectively. CNPq also provided research grants to E.C. Gavioli, N.S. Canteras, and T.C.M. De Lima. The authors would like to thank Dr. Gareth Cuttle for the final English revision of the text.

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Authors and Affiliations

  1. Department of Pharmacology, CCB, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil

    Filipe Silveira Duarte, Marcelo Duzzioni, Alexandre Ademar Hoeller & Thereza Christina Monteiro De Lima

  2. Federal University of Rio Grande do Norte, Natal, RN, Brazil

    Elaine Cristina Gavioli

  3. Department of Anatomy, ICB, University of São Paulo, São Paulo, SP, Brazil

    Newton Sabino Canteras

  4. Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88049-900, Brazil

    Thereza Christina Monteiro De Lima

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  1. Filipe Silveira Duarte
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  2. Elaine Cristina Gavioli
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Correspondence to Thereza Christina Monteiro De Lima.

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Duarte, F.S., Gavioli, E.C., Duzzioni, M. et al. 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. Psychopharmacology 212, 653–661 (2010). https://doi.org/10.1007/s00213-010-1985-6

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  • DOI: https://doi.org/10.1007/s00213-010-1985-6

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