Summary: A drug that blocks the alpha7 nicotinic acetylcholine receptor may provide a new method for combating drug addiction relapse, researchers report.
Source: University of Bath.
Research published in Addiction Biology by scientists at the University of Bath reveals a new potential mechanism for combatting drug addiction relapse.
Relapsing into drug taking is a big problem in treating addiction, where the majority of addicts return to drug-taking within 12 months of quitting. This is brought into focus by the burgeoning ‘opioid epidemic’ of prescription as well as recreational opioid drugs, such as morphine and heroin. Addiction relapse is associated with drug-related cues such as places, drug paraphernalia, the drug itself, or stress, highlighting that memories play a key role in addiction relapse.
In this study researchers at Bath, working with colleagues from the University of Surrey and RenaSci, used an animal model to study relapse to morphine seeking behaviour. Rats or mice learned to associate particular environmental cues with morphine. After removal of the drugs, relapse back to drug-seeking behaviour occurred in response to getting the cues again.
The Bath team wanted to test the effect of using a blocker for a brain neurotransmitter called acetylcholine, which is involved in memory processes. They tested the effect of a blocker of a specific receptor for acetylcholine – the alpha7 nicotinic receptor – to see if this might impair relapse. This drug, methyllycaconitine (MLA), that comes from Delphinium plants, selectively blocked morphine relapse (but not the initial learning to seek drugs), in both mice and rats.
This exciting novel observation led the researchers to investigate the brain region responsible for MLA’s effect and identified the ventral hippocampus as the locus. The hippocampus is well known for its role in memory, and the ventral domain is particularly associated with emotional memories, an obvious link to addiction pathways.
Professor Sue Wonnacott, from the University of Bath’s Department of Biology & Biochemistry, said: “It’s an exciting step forward that links the cholinergic system, more commonly associated with nicotine addiction, with the mechanisms of relapse a different class of abused drug – the opioids. More work needs to be done to uncover the brain mechanisms involved, but it raises the prospect of erasing long-term drug-associated memories that underpin addiction and the propensity to relapse.”
Dr Chris Bailey, from the University of Bath’s Department of Pharmacy & Pharmacology, commented: “Drug addiction is very poorly treated at present so this potential novel approach is very welcome. An important next step is to see if MLA blocks relapse to other abused drugs. We already have evidence, in the same animal model, that it is effective against the more potent opioid, heroin. If MLA has similar effects against other drugs of abuse such as cocaine it would be even more encouraging.”
Funding: The research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and RenaSci.
Source: Chris Melvin – University of Bath
Publisher: Organized by NeuroscienceNews.com.
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Original Research: Open access research for “Inhibition of alpha7 nicotinic receptors in the ventral hippocampus selectively attenuates reinstatement of morphine‐conditioned place preference and associated changes in AMPA receptor binding” by Victoria L. Wright, Polymnia Georgiou, Alexis Bailey, David J. Heal, Christopher P. Bailey, and Susan Wonnacott in Addiction Biology. Published April 17 2018
Inhibition of alpha7 nicotinic receptors in the ventral hippocampus selectively attenuates reinstatement of morphine‐conditioned place preference and associated changes in AMPA receptor binding
Recurrent relapse is a major problem in treating opiate addiction. Pavlovian conditioning plays a role in recurrent relapse whereby exposure to cues learned during drug intake can precipitate relapse to drug taking. α7 nicotinic acetylcholine receptors (nAChRs) have been implicated in attentional aspects of cognition and mechanisms of learning and memory. In this study we have investigated the role of α7 nAChRs in morphine‐conditioned place preference (morphine‐CPP). CPP provides a model of associative learning that is pertinent to associative aspects of drug dependence. The α7 nAChR antagonist methyllycaconitine (MLA; 4 mg/kg s.c.) had no effect on the acquisition, maintenance, reconsolidation or extinction of morphine‐CPP but selectively attenuated morphine‐primed reinstatement of CPP, in both mice and rats. Reinstatement of morphine‐CPP in mice was accompanied by a selective increase in [3H]‐AMPA binding (but not in [3H]‐MK801 binding) in the ventral hippocampus that was prevented by prior treatment with MLA. Administration of MLA (6.7 μg) directly into the ventral hippocampus of rats prior to a systemic priming dose of morphine abolished reinstatement of morphine‐CPP, whereas MLA delivered into the dorsal hippocampus or prefrontal cortex was without effect. These results suggest that α7 nAChRs in the ventral hippocampus play a specific role in the retrieval of associative drug memories following a period of extinction, making them potential targets for the prevention of relapse.