Cracking the molecular code of cocaine addiction.

S. H. Ahmed, P. J. Kenny
ILAR Journal. 2011-01-01; 52(3): 309-320
DOI: 10.1093/ilar.52.3.309

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1. ILAR J. 2011;52(3):309-20. doi: 10.1093/ilar.52.3.309.

Cracking the molecular code of cocaine addiction.

Ahmed SH, Kenny PJ.

Cocaine addiction is a behavioral disorder defined by behavioral symptoms that
set it apart from nondisordered forms of drug use. Here we review evidence in
rats (the most frequently used animal model in the field) that it is possible,
after extended (but not after limited) access to cocaine for self-administration,
to selectively induce some of these behaviors: gradual escalation of cocaine
intake, enhanced motivation for the drug despite increased costs (or negative
consequences), and increased sensitivity to drug- and stress-primed craving-like
behavior. Animals with extended drug use also present selective neurocognitive
deficits (e.g., compromised working memory) that may impair their ability to
regulate cocaine intake. In some rats, extended access to cocaine for
self-administration is associated with loss of control over cocaine intake, as
assessed by continued drug use despite the opportunity to make a different choice
and to the exclusion of more natural and rewarding activities. These rats may
represent the most advanced and severe stage on the path to cocaine addiction.
Finally, comparisons of rats with extended versus limited access to cocaine for
self-administration have recently revealed the existence of a new molecular
pathway in the dorsal striatum (a brain region altered in cocaine-addicted
humans) that causally and selectively controls cocaine intake. This pathway
involves unforeseen homeostatic interactions between microRNAs (a class of
nonprotein-coding RNAs) and some key molecular regulators of neuronal plasticity
(e.g., MeCP2 and BDNF). This discovery provides an entirely new direction for the
development of effective antiaddiction treatments.

DOI: 10.1093/ilar.52.3.309
PMID: 23382145 [Indexed for MEDLINE]

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