Behavioral depression in the swim test causes a biphasic, long-lasting change in accumbens acetylcholine release, with partial compensation by acetylcholinesterase and muscarinic-1 receptors.

Full Abstract

The nucleus accumbens may play a role in acquisition and expression of behavioral depression as measured using the inescapable swim test. Previous work shows that a local injection of a cholinergic muscarinic-1 receptor agonist increases immobility and a specific muscarinic-1 antagonist acts as an antidepressant-like drug by increasing swimming escape efforts. The present study used microdialysis to monitor extracellular acetylcholine levels in the accumbens, fluorescent labeled toxins to monitor changes in acetylcholinesterase and muscarinic-1 receptors, and semiquantitative-polymerase chain reaction to detect changes in gene expression for the muscarinic-1 receptor. Microdialysis showed that acetylcholine levels did not change while an animal was swimming; however, a significant transient decrease occurred when the rat was returned to the dialysis cage, followed by a long-lasting increase that reached a maximum three hours after the test. Acetylcholine levels stayed high even 24 h after the initial test as evidenced by a significant elevation in basal level prior to the second swim. This increase in neurotransmitter may have been partially compensated by a significant increase in the degradative enzyme, acetylcholinesterase, and by a decrease in muscarinic-1 receptors and their gene expression. These results further demonstrate the importance of accumbens cholinergic function in the appearance of a depression-like state.

Author information

Author/s: Rada, P (P); Colasante, C (C); Skirzewski, M (M); Hernandez, L (L); Hoebel, B (B);

Affiliation: Laboratory of Behavioral Physiology, Medical School, University of Los Andes, Merida, Venezuela. radap(-atsign-)ula.ve

Grants: DA 10608 (Agency:NIDA NIH HHS) ; MH 65024 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)

Reference: 2006-Aug; vol 141 (issue 1) : pp 67-76

Dates: Created 2006/07/03; Completed 2006/09/28; Revised 2007/11/14;

PMID: 16677771, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

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