Brendan M. Walker, Ph.D.
My long-term research interest has been the neurobiology of motivational systems and how acute and long-term alcohol (and other drugs of abuse such as heroin) impact brain reward systems to promote increased drug seeking and consumption. Utilizing a combination of behavioral, anatomical, pharmacological, immunohistochemical, molecular and genetic approaches, we are currently evaluating the neuroadaptations produced by chronic ethanol and opioid exposure that promote enhanced intake of these abused compounds. This excessive intake is hypothesized to reflect the development of negative reinforcement (learning about the reinforcing (response increasing) nature of aversive stimulus removal that occurs when alcohol and drugs are consumed to relieve acute and protracted withdrawal symptoms) processes that compliment positive reinforcement processes governing non-dependent intake that developed earlier in life. Consequently, we are extremely interested in dependence-induced depression and anxiety because they appear to be lay the foundation for the observed increases in the negative reinforcing properties of abused substances. As an extension of this work, we also focus on the morphological and molecular mechanisms of plasticity associated with negative reinforcement learning. The lab is also investigating differences in impulsivity produced by chronic alcohol and drug exposure, as well as, animal models of adolescent alcohol and drug exposure that impact adult alcohol and drug intake. Once enough information is gathered about the nature of the brain’s response to chronic alcohol and drug exposure, that information can be used to help develop pharmacotherapies for the treatment of alcohol and drug addiction.
Walker BM, Kissler JL (2013): Dissociable Effects of Kappa-Opioid Receptor Activation on Impulsive Phenotypes in Wistar Rats. Neuropsychopharmacology, doi: 10.1038/npp.2013.129.
Kissler JL, Sirohi S, Reis DJ, Jansen HT, Quock RM, Smith DG, Walker BM (2013). The One-Two Punch of Alcoholism: Role of Central Amygdala Dynorphins/Kappa-Opioid Receptors. Biological Psychiatry, doi: 10.1016/j.biopsych.2013.03.014.
Berger AL, Williams AM, McGinnis MM, Walker BM (2013). Affective Cue-Induced Escalation of Alcohol Self-Administration and Increased 22-kHz Ultrasonic Vocalizations during Alcohol Withdrawal: Role of Kappa-Opioid Receptors. Neuropsychopharmacology 38: 647-654.
Sirohi S, Bakalkin G and Walker BM (2012). Alcohol-induced plasticity in the dynorphin / kappa-opioid receptor system. Frontiers in Molecular Neuroscience doi: 10.3389/fnmol.2012. 00095.
Williams AM, Reis DJ, Powell AS; Neira LJ, Nealey KA, Ziegler CE, Kloss N, Bilimoria JL, Smith CE and Walker BM (2012). The Effect of Intermittent Alcohol Vapor or Pulsatile Heroin on Somatic and Negative Affective Indices during Spontaneous Withdrawal in Wistar Rats. Psychopharmacology, 223, 1, 75-88.
Walker BM (2012). Conceptualizing Withdrawal-Induced Escalation of Alcohol Self-Administration as a Learned, Plasticity-Dependent Process. Alcohol, 46, 4, 339-348.
Walker BM, Valdez GR, McLaughlin JP and Bakalkin G (2012). Targeting dynorphin / kappa-opioid receptor systems to treat alcohol abuse and dependence. Alcohol, 46, 4, 359-370.
Smith AW, Nealey KA, Wright JW and Walker BM (2011). 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, 96, 199-206.
Nealey KA, Smith AW, Davis SM, Smith DG and Walker BM (2011). K-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology, 61, 35-42
Walker BM, Zorrilla EP, Koob GF (2011). Systemic K-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats. Addiction Biology, 16, 1, 116-119.
Walker JL, Walker BM, Fuentes FM, Rector DM (2011). Rat psychomotor vigilance task with fast response times using a conditioned lick behavior. Behavioural Brain Research, 216, 1, 229-237.
Walker BM, Drimmer DA, Walker JL, Liu T, Mathe AA, Ehlers CE (2010). Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin releasing factor levels in rat brains. Alcohol, 44, 6, 487-493.