Journal article
Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems
Neurobiology of learning and memory, Vol.96(2), pp.199-206
09/2011
Handle:
https://hdl.handle.net/2376/101135
PMCID: PMC3148339
PMID: 21530666
Abstract
► Intermittent ethanol vapor exposure resulted in escalated operant self-administration for ethanol during acute withdrawal in dependent animals. ► Chronic matrix metalloproteinase (MMP) inhibition during the dependence induction period and acute withdrawal post-dependence testing prevented escalated ethanol self-administration. ► Dependence-induced escalation was shown to be a learned, plasticity-dependent, response because acute MMP inhibition prevented escalated ethanol self-administration.
Repeated cycles of ethanol intoxication and withdrawal associated with dependence induce neuroadaptations in a variety of brain systems. Withdrawal-induced negative emotional states can be ameliorated by ethanol consumption; a learned process termed negative reinforcement. Accordingly, a dependence-induced phenotype is escalated ethanol self-administration. Matrix metalloproteinases (MMPs) are proteolytic enzymes which degrade the extracellular matrix to allow for synaptic reorganization and plasticity. To test the hypothesis that an intact MMP system is required for animals to learn about the negative reinforcing effects of ethanol and display escalated self-administration during acute withdrawal when ethanol-dependent, male Wistar rats were trained to self-administer ethanol and then assigned to either acute or chronic MMP inhibition treatment groups. The chronic treatment group received intracerebroventricular (ICV) infusions of the broad spectrum MMP inhibitor FN-439 or artificial cerebrospinal fluid (aCSF) via osmotic minipumps during a 1month ethanol dependence induction period and subsequent post-dependence induction self-administration sessions that occurred during acute withdrawal. The acute treatment group only received ICV FN-439 or aCSF on the day of self-administration sessions following dependence induction during acute withdrawal. The results showed that inhibition of MMPs attenuated escalated ethanol self-administration following chronic and acute exposure conditions. Furthermore, once learning (i.e., plasticity) had occurred, MMP inhibition had no impact on escalated response patterns and animals previously subjected to MMP inhibition that did not escalate evidenced normal escalations in operant ethanol self-administration once FN-439 treatments were terminated. Thus, the present data identified that an intact MMP system is required for the escalated responding that occurs during acute withdrawal in dependent animals and implicate such escalation as a learned response.
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Details
- Title
- Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems
- Creators
- Alexander W Smith - Department of Psychology, Washington State University, Pullman, WA, USAKathryn A Nealey - Department of Psychology, Washington State University, Pullman, WA, USAJohn W Wright - Department of Psychology, Washington State University, Pullman, WA, USABrendan M Walker - Department of Psychology, Washington State University, Pullman, WA, USA
- Publication Details
- Neurobiology of learning and memory, Vol.96(2), pp.199-206
- Academic Unit
- Psychology, Department of; Integrative Physiology and Neuroscience, Department of
- Publisher
- Elsevier Inc
- Identifiers
- 99900546697201842
- Language
- English
- Resource Type
- Journal article