Title

Promnestic Effects of Intranasally Applied Pregnenolone in Rats

Document Type

Article

Publication Date

9-2016

Publication Title

Neurobiology of Learning and Memory

Keywords

Intranasal drug administration, Neuroseroid, Pregnenolone, Memory, Water maze, Object recognition

ISSN

1074-7427

Volume

133

First Page

185

Last Page

195

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.

Comments

©2016 Elsevier Inc. All rights reserved.

Additional Comments

Heisenberg Fellowship grant #: DFG SO 1032/5-1; EU-FP7 grant #: MC-ITN-"In-SENS"-ESR7 607616; Deutsche Forschungsgemeinschaft grant #: HU 306/27-3

DOI

10.1016/j.nlm.2016.07.012

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