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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    818—Opioid Reinforcement, Seeking, and Reinstatement

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    818.10: The effect of an animal conflict model of drug addiction on perineuronal nets

    Location: Halls B-H

    *P. CHU1,3, J. PECK4,3, E. KARIYEVA4, R. ABRAHAM5, U. KHAN4, R. RANALDI2,3, J. C. BRUMBERG2,3;
    2Psychology, 1Queens College, City Univ. of New York, Flushing, NY; 3The Grad. Center, CUNY, Ny, NY; 4Psychology, 5Neurosci. Program, Queens College, City Universty of New York, Flushing, NY

    Abstract Body: Perineuronal nets (PNNs) are ubiquitous extracellular matrix aggregates of proteins and proteoglycans ensheathing the outer membranes of neurons. These molecules likely play a role in inhibiting plasticity in the brain and spinal cord as there maturation coincides with the closing of developmental sensitive periods . Further, preventing normal sensory inputs to the brain via sensory deprivation during early development attenuates their normal mature expression levels in the somatosensory and visual cortex. Enzymatically digesting away PNN components beyond this sensitive period has been shown to recover juvenile levels of plasticity that are normally not seen in adulthood. However, changes to the expression levels of PNNs have not been well studied in the context of complex behaviors such as those occurring during drug addiction. We trained adult male Long-Evans rats to self administer heroin, induced abstinence in the presence of a punishing stimulus (electric floor shock) and measured the degree of relapse in the presence of a non-contingent drug cue. We labeled 33 anatomical regions in these rats with Wisteria Floribunda Agglutinin and compared them to naïve controls and found complex outcomes with reductions in PNN ranging from about 5% to over 90%. Most of the regions examined (75%) showed reductions between 50%-75% relative to control including the somatosensory cortex, motor cortex and insula. The magnitude of these effects may reflect changes to specific neural circuits during complex events such as drug addiction, punishment and abstinence.

    Lay Language Summary: Complex neural events occur during heroin use, abstinence and relapse which can exert global changes to the brain, even in regions that have not been traditionally implicated with drug addiction. Using a novel rodent model that mimics the human condition of drug abuse, we determined that molecules surrounding the extracellular surface of neuronal membranes (perineuronal nets) are reduced in the brain following drug addiction. These molecules have been previously implicated in regulating learning, as their disruption in adult’s results in reactivation of a highly malleable brain period that is only present in youth.
    To study this, we used a drug abstinence model that captures the important features of abstinence reported in humans where there are negative consequences of drug seeking. We have shown that abstinence can be forced when an electric floor barrier stands between rats and their access to heroin. However, when presented with an environmental cue for the drug, that they will consistently relapse despite the painful barrier to drug access. In the current work, we analyzed the brains of these animals by labeling perineuronal nets throughout the brain and noted a significant correlation where increased drug intake resulted in the reduced presence of these nets around neurons.
    The focus of traditional drug addiction research focuses on brain regions that are evolutionarily older. These brain regions are involved in reward and are usually hijacked by drugs of abuse. Our research suggests that perineuronal nets which are attached to the outside of a special class of inhibitory neuron found in the cerebral cortex, a more recently evolved brain area, may play a role in drug abuse. Clinically, this opens up the possibility for possibly targeting this cell type in future therapeutic approaches. In addition, our research emphasizes the need to use animal models that more closely reflect the human condition and to examine regional brain changes that may contribute to maintaining addiction by affecting cognitive/affective control and perhaps even change sensory-motor circuits to maintain addiction.
    Looking forward, we will seek to thoroughly test a treatment paradigm which focuses on providing an enriched living environment as a counter to the rewarding effects of drugs. Consistent with previous reports our preliminary data show that an enriched living environment lead to early and prolonged abstinence in drug seeking rats using the same conflict abstinence/relapse model and that enrichment confers some degree of protection on perineuronal net expression in multiple brain regions.
    Every year, abuse of illicit drugs, tobacco and alcohol contributes to the death of more than 500,000 Americans. Consequently, a tremendous amount of resources have been devoted to the development of pharmacotherapies for drug addiction, with relatively little or no long term success being reported. Thus, animal models of drug addiction that examine the effects of drugs on the brain are critical in the development and early phase testing of drug treatment methods that could lead to successful long-term abstinence in humans. Importantly, there is a critical need to target other possible brain mechanisms (e.g. perineuronal nets) that have not yet been explored in the development of traditional drug abuse treatments.