Special Issue "Addiction and Neuroadaptation"

Guest Editor
Dr. Marcelo Febo
Department of Psychiatry, Director of Translational Research Imaging, The McKnight Brain Institute, University of Florida, 100 S. Newell Dr. L4-100F, Gainesville, FL 32611, USA
Website: http://psychiatry.ufl.edu/Faculty-And-Staff/Directories/Faculty/Febo-Marcelo/
E-Mail: febo@ufl.edu
Phone: +1 352 294 4911
Interests: functional magnetic resonance imaging of awake animals; neuropeoptide modulation of maternal care in rats

Dear Colleagues,

One of the defining features of drug addiction is the high rate of relapse to drug seeking and taking even after prolonged abstinence periods. Regressing towards drug intake in spite of the negative consequences, and the inability to control intake, strongly suggests that the brain undergoes enduring and perhaps permanent neurobiological changes that need to be fully understood before effective treatments are established. Advancements in our knowledge of the biological underpinnings of addictive disorders have greatly increased over the past decade. Animal studies modeling distinct phases such as sustained drug intake, withdrawal, extinction and relapse are instrumental to gaining insight on neurobiological mechanisms. This has been accompanied by conceptual shifts in our understanding of the control of gene expression, discoveries of the synaptic and molecular events involved in long-term plasticity and memory, and developments of translational neuroimaging tools that provide a global view of brain activity and brain structural changes. This special issue will bring together original research and review articles on the neural correlates of addiction, primarily focused on ‘neuroadaptive mechanisms’ and how these brain changes may impact behavior even after protracted abstinence. More studies using specialized techniques to probe in vivo brain activity, unique animal models to correlate neural substrates and behavior, and articles introducing novel concepts and discoveries are needed to further expand the breadth of our current knowledge of this disease impacting society on a global scale.

Dr. Marcelo Febo
Guest Editor

Submission

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• addiction
• drug
• reward
• drug abuse
• animal models
• neuroimaging
• reinforcer
• conditioning
• memory
• plasticity
• gene expression
• molecular
• neuroadaptations

Type of Paper: Article
Title: The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Addiction in Rats
Authors: John W. Wright ¹, Wendy L. Wilson ², Vanessa Wakeling ¹, Alan S. Boydstun ³, Audrey Jensen ¹, Leen Kawas ⁴ and Joseph W. Harding ^1,4
Affiliations: ¹ Departments of Psychology, and Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164-4820, USA; E-Mail: wrightjw@wsu.edu (J.W.W.)
² Department of Psychology, Dickinson State University, Dickinson, ND, USA
³ L-3 Communications: Link Simulation and Training 2620 Q Street, Wright Patterson Air Force Base, OH 45433-7955, USA
⁴ Program in Pharmacology and Toxicology, Washington State University, Pullman, WA 99164-4820, USA
Abstract: The use of methamphetamine (MA) is increasing in the U.S. and elsewhere around the world. MA’s capacity to cause addiction in man and animals significantly exceeds other psychostimulant drugs, and its use negatively impacts learning and memory. Recently attempts have been made to interfere with the presumed mechanism(s) underlying the establishment of drug-induced memory consolidation. The majority of these studies have employed matrix metalloproteinase (MMP) inhibitors to disrupt MMP-induced extracellular matrix molecule dependent synaptic reconfiguration, or GABA_B receptor blockers. The present investigation utilized an angiotensin IV (AngIV) analogue, Divalinal-AngIV (divalinal), to disrupt acquisition of MA addiction in rats as measured using the conditioned place preference paradigm. Results indicate that both acute and chronic intracerebroventricular infusion of divalinal prior to each daily subcutaneous injection of MA prevented addiction. However, divalinal was unable to prevent MA-induced reinstatement after the prior acquisition of addiction followed by extinction trials. These results indicate that prevention of MA addiction can be accomplished by blockade of the brain AT₄ receptor subtype. On the other hand, once MA addiction-induced memory consolidation is in place divalinal appears to be ineffective. Mechanistic studies indicated that divalinal is a potent inhibitor of the hepatocyte growth factor (HGF)/c-Met system, and thus a functional HGF/c-Met system appears to be required for the acquisition of MA-mediated addiction.
Keywords: methamphetamine; conditioned place preference; angiotensin IV; divalinal-AngIV; hepatocyte growth factor; AT₄ receptor; c-Met receptor

Type of Paper: Article
Title: The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats
Authors: Colin N. Haile, Hao Yanli, Patrick O’Malley, Thomas F. Newton and Therese A. Kosten
Affiliation: Department of Psychiatry, Baylor College of Medicine, and Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA; E-Mail: tkosten@bcm.edu (T.A.K.)
Abstract: Medications that target norepinephrine (NE) neurotransmission alter the behavioral effects of cocaine and may be beneficial to treat addiction. Previously, we showed that the short-acting, α1-adrenergic antagonist, prazosin, blocked drug-induced reinstatement of cocaine-seeking in rats. Subsequently, we demonstrated that doxazosin (DOX) blocked cocaine’s subjective effects in cocaine-dependent non-treatment seeking volunteers. DOX is a longer-acting α1 antagonist than prazosin and therefore, may be more useful clinically. To further characterize DOX as a possible pharmacotherapy for cocaine dependence, we assessed its impact on the development and expression of cocaine-induced locomotor sensitization in rats. Rats (n = 6–8) were administered saline, cocaine (COC, 10mg/kg) or DOX (0.3 and 1.0 mg/kg) alone or in combination for 5 consecutive days (development). Following 10-days of drug withdrawal, all rats were administered COC and locomotor activity was again assessed (expression). As expected, COC increased locomotor activity across days indicative of sensitization. Both doses of DOX in combination with COC significantly decreased the development of sensitization. DOX alone did not differ from the effects of saline. On the test of expression, rats treated with COC+DOX or DOX alone had significantly lower locomotor activity compared to the COC alone group. These results are consistent with previous studies indicating that the NEergic system, α1 receptors in particular, are essential for the development and expression of cocaine’s behavioral effects. Results also suggest that the locomotor sensitization paradigm employed in this study may have predictive validity in assessing possible pharmacotherapies for cocaine dependence in humans.

Type of Paper: Article
Title: Cortical and Sub-Cortical Grey Matter Changes in Active Methamphetamine Users
Authors: Reem K. Jan ^1,2, Joanne C. Lin ^1,2, Rob R. Kydd ^2,3 and Bruce R. Russell ^1,2
Affiliations: ¹ School of Pharmacy, University of Auckland, Private Bag 92019, Auckland, New Zealand; E-Mail: r.jan@auckland.ac.nz (R.K.J.)
² Psychopharmacology & Neurodynamics Group, Centre for Brain Research, Faculty of Medical & Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
³ Department of Psychological Medicine, Faculty of Medical & Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
Abstract: The effect of methamphetamine dependence on the structure of the human brain has not been extensively studied. This study aimed to investigate structural grey matter (GM) changes in the brains of active methamphetamine users. Seventeen active methamphetamine‐dependent participants and 20 healthy controls aged 18–46 years underwent magnetic resonance imaging using a 1.5T system. Significant GM reductions were observed in the left superior and right superior/middle frontal gyri of methamphetamine users, which correlated with poorer performance during memory recall, sensorimotor and attention tasks. In contrast, there were GM density gains in the bilateral putamen of methamphetamine users which correlated with improved performance during tasks of attention and executive function. In conclusion, active chronic methamphetamine use was associated with cortical GM deficits which correlated with poorer cognitive function; in contrast striatal enlargement may have occurred as a compensatory response to maintain cognitive function.