Central amygdala nicotinic and 5-HT1A receptors mediate the reversal effect of nicotine and MDMA on morphine-induced amnesia.
F Tirgar, A Rezayof, M-R Zarrindast
Neuroscience September 26, 2014 DOI: 10.1016/j.neuroscience.2014.07.014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Adult male Wistar rats |
| Interventions | Morphine Nicotine MDMA Mecamylamine (S)-WAY 100135 |
| Dose | morphine 3-7 mg/kg; nicotine 0.3 and 0.5 mg/kg, and 0.1 mg/kg; MDMA 1-2 µg/rat; mecamylamine 1-2 µg/rat; (S)-WAY 100135 0.25-1 µg/rat |
| Measures | step-through passive avoidance task |
| Topics | MDMA Serotonin |
| Keywords | Drugs of abuse Memory retrieval Rats |
| Key findings | The authors conclude that morphine, nicotine, and MDMA interact functionally in the central amygdala via nicotinic and 5-HT1A receptor mechanisms to influence passive avoidance memory retrieval, and propose that cross state-dependent memory retrieval may occur between these drugs, possibly depending on their rewarding effects. |
Abstract
The present study was designed to investigate possible involvement of the central amygdala (CeA) nicotinic acetylcholine (nACh) and 5-hydroxytryptamine 1A (5-HT1A) receptors in the reversal effect of nicotine and 3,4-methylenedioxy-N-methylamphetamine (MDMA or ecstasy) on morphine-induced amnesia. Two guide cannulas were stereotaxically implanted in the CeA regions and a step-through passive avoidance task was used for the assessment of memory retrieval in adult male Wistar rats. Our results indicated that post-training s.c. administration of morphine (3-7-mg/kg) impaired memory retrieval. Pre-test administration of nicotine (0.3- and 0.5-mg/kg, s.c.) reversed morphine-induced amnesia. In addition, pre-test intra-CeA injection of MDMA (1-2-μg/rat) with an ineffective dose of nicotine (0.1-mg/kg, s.c.) improved memory retrieval, suggesting the interactive effect of the drugs on memory formation. It should be noted that that pre-test intra-CeA injection of 2-μg/rat of MDMA by itself produced amnesia. Interestingly, pre-test intra-CeA injection of mecamylamine, a nACh receptor antagonist (1-2-μg/rat) or (S)-WAY 100135 (0.25-1-μg/rat), a selective 5-HT1A receptor antagonist inhibited the improvement of morphine-induced amnesia which was produced by pre-test co-injection of nicotine and MDMA. Pre-test intra-CeA injection of the same doses of MDMA, mecamylamine or (S)-WAY 100135 by itself had no effect on morphine-induced amnesia. Moreover, pre-test injection of the same doses of mecamylamine or (S)-WAY 100135 into the CeA alone could not change memory retrieval. Taken together, it can be concluded that there is a functional interaction between morphine, nicotine and MDMA via the CeA nicotinic and serotonergic receptor mechanisms in passive avoidance memory retrieval. Moreover, cross state-dependent memory retrieval may have been induced between the drugs and this probably depends on the rewarding effects of the drugs.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 12
- Mood and cognitive effects of ± 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’): week‐end ‘high’ followed by mid‐week low Addiction July 1, 1997
- MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress Journal of Psychopharmacology March 1, 2006
- MDMA (‘ecstasy’) enhances basal acetylcholine release in brain slices of the rat striatum European Journal of Neuroscience April 1, 2000
- Investigation of serotonin-1A receptor function in the human psychopharmacology of MDMA Journal of Psychopharmacology July 17, 2008
- MDMA and 5‐HT neurotoxicity: the empirical evidence for its adverse effects in humans – no need for translation British Journal of Pharmacology March 9, 2012
and 7 more in the library