Abstract
The neurosteroid pregnenolone (PREG) has been shown to have memory-enhancing and anti-depressant action. The present study addresses the question of whether intranasally applied pregnenolone (IN-PREG) also has promnestic properties in the rat. We examined the effects of IN-PREG at doses of 0.187 and 0.373 mg/kg on memory for objects and their location on learning and retention of escape in a water maze, and on behavior on the elevated plus maze. The main findings were: (a) Pre-trial, but not post-trial, administration of IN-PREG facilitated long-term memory in a novel object-preference test and a novel object-location preference test when tested 48 h after dosing. (b) Over the duration of 5 days of extinction trials, after learning to escape onto a hidden platform in a water maze, the animals treated with IN-PREG spent more time in searching for the absent platform, indicating either, or both, superior memory for the former position of the escape platform, or a higher resistance to extinction. (c) Administration of the anticholinergic, scopolamine, disrupted learning to escape from the water maze in the vehicle-treated group. The IN-PREG treated groups exhibited superior escape learning in comparison with vehicle controls, indicating that the treatment countered the scopolamine effect. IN-PREG treatment had no influence on behaviors on the elevated plus maze. Our results demonstrate that IN-PREG is behaviorally active with cognitive enhancing properties comparable to those known from studies employing systemic PREG administration.
Original language | English (US) |
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Pages (from-to) | 185-195 |
Number of pages | 11 |
Journal | Neurobiology of Learning and Memory |
Volume | 133 |
DOIs | |
State | Published - Sep 1 2016 |
Externally published | Yes |
Bibliographical note
Funding Information:M.A. de Souza Silva was supported by a Heisenberg Fellowship DFG SO 1032/5-1 and EU-FP7 (MC-ITN-“In-SENS”-ESR7 607616). J.P. Huston was supported by “ Deutsche Forschungsgemeinschaft ” Grant ( HU 306/27-3 ). L. Abdel-Hafiz received support from the DAAD (German Academic Exchange Program).
Publisher Copyright:
© 2016 Elsevier Inc.
Keywords
- Intranasal drug administration
- Memory
- Neurosteroid
- Object recognition
- Pregnenolone
- Water maze