Effects of muscarinic M1 and M4 acetylcholine receptor stimulation on extinction and reinstatement of cocaine seeking in male mice, independent of extinction learning

Effects of muscarinic M1 and M4 acetylcholine receptor stimulation on extinction and... Rationale Stimulating muscarinic M /M receptors can blunt reinforcing and other effects of cocaine. A hallmark of addiction is 1 4 continued drug seeking/craving after abstinence and relapse. Objectives We tested whether stimulating M and/or M receptors could facilitate extinction of cocaine seeking, and whether this 1 4 was mediated via memory consolidation. Methods Experimentally naïve C57BL/6J mice were allowed to acquire self-administration of intravenous cocaine (1 mg/kg/ infusion) under a fixed-ratio 1 schedule of reinforcement. Then, saline was substituted for cocaine until responding extinguished to ≤30% of cocaine-reinforced responding. Immediately after each extinction session, mice received saline, the M /M receptor- 1 4 preferring agonist xanomeline, the M receptor-selective allosteric agonist VU0357017, the M receptor-selective positive 1 4 allosteric modulator VU0152100, or VU0357017 + VU0152100. In additional experiments, xanomeline was administered delayed after the session or in the home cage before extinction training began. In the latter group, reinstatement of responding by a 10-mg/kg cocaine injection was also tested. Results Stimulating M +M receptors significantly expedited extinction from 17.2 sessions to 8.3 using xanomeline or 7.8 using 1 4 VU0357017 + VU0152100. VU0357017 alone and VU0152100 alone did not significantly modify rates of extinction (12.6 and 14.6 sessions). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Effects of muscarinic M1 and M4 acetylcholine receptor stimulation on extinction and reinstatement of cocaine seeking in male mice, independent of extinction learning

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Publisher
Springer Journals
Copyright
Copyright © 2017 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Biomedicine; Neurosciences; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
D.O.I.
10.1007/s00213-017-4797-0
Publisher site
See Article on Publisher Site

Abstract

Rationale Stimulating muscarinic M /M receptors can blunt reinforcing and other effects of cocaine. A hallmark of addiction is 1 4 continued drug seeking/craving after abstinence and relapse. Objectives We tested whether stimulating M and/or M receptors could facilitate extinction of cocaine seeking, and whether this 1 4 was mediated via memory consolidation. Methods Experimentally naïve C57BL/6J mice were allowed to acquire self-administration of intravenous cocaine (1 mg/kg/ infusion) under a fixed-ratio 1 schedule of reinforcement. Then, saline was substituted for cocaine until responding extinguished to ≤30% of cocaine-reinforced responding. Immediately after each extinction session, mice received saline, the M /M receptor- 1 4 preferring agonist xanomeline, the M receptor-selective allosteric agonist VU0357017, the M receptor-selective positive 1 4 allosteric modulator VU0152100, or VU0357017 + VU0152100. In additional experiments, xanomeline was administered delayed after the session or in the home cage before extinction training began. In the latter group, reinstatement of responding by a 10-mg/kg cocaine injection was also tested. Results Stimulating M +M receptors significantly expedited extinction from 17.2 sessions to 8.3 using xanomeline or 7.8 using 1 4 VU0357017 + VU0152100. VU0357017 alone and VU0152100 alone did not significantly modify rates of extinction (12.6 and 14.6 sessions).

Journal

PsychopharmacologySpringer Journals

Published: Dec 18, 2017

References

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