brain

(Jörgen Engel, Lennart Svensson, Gun Andersson, Kenn Johannessen, Mariann Nyqvist, Daniel Klamer, Elisabet Jerlhag, Erik Pålsson, Caroline Wass, Kim Fejgin)




joergen engel Jörgen A Engel, MD, PhD
Professor of Pharmacology
Recipient of the 2001 Salus Ansvar Prize for Outstanding Scientific Achievement in Biomedical Alcohol Research





RESEARCH INTEREST

Our major research interest is in the field of neuropsychopharmacology. The research can be broken down into two main projects:


THE NEUROBIOLOGY OF ADDICTION

The long-term objective of this project is to gain insight into the neuronal mechanisms underlying the dependence producing properties of ethanol and other dependence-producing drugs, especially how multiple neurotransmitters collectively orchestrate the reward profile of ethanol (see figure). With the knowledge obtained we aim at developing new pharmacological treatment strategies for addiction. Currently our research is focused on integrated preclinical and clinical studies on the interaction between alcohol and nicotine.

Brain Symphony


Our research is based on the following metaphor. In the brain there is a symphony orchestra that can play the reward symphony. The different neurotransmitters are regarded as the various instruments in the orchestra. Every instrument can play the reward tune but only when all the instruments play together, in this case with alcohol as the invited conductor, can the reward symphony be fully appreciated. The final appreciation of the reward symphony is dependent on factors related to the individual and those are not only of genetic nature, but also the age and hormonal state of the individual and last but not least environmental factors are of great importance for how the reward symphony is experienced.


THE NEUROBIOLOGY OF SCHIZOPHRENIA

This project aims to elucidate the neural and neurochemical substrates underpinning cognitive processes in the brain and how these contribute to fundamental schizophrenic cognitive disturbances. Understanding the neurobiology of cognitive dysfunctions may open up new avenues of research into the management and treatment of schizophrenia. We are mainly using the prepulse inhibition of acoustic startle paradigm (a model of pre-attentive information processing in the brain, a measure shown diminished in schizophrenic persons), to investigate the pathophysiological processes involved in schizophrenia (see figure). Furthermore, by using models for early brain development disturbances, which result in deficits in pre-attentive information processing in the adult animal, we hope to point out means by which genetical and early environmental factors may promote the development of schizophrenia. The research is presently focused on 1) the pharmacological characterization of sensorimotor function, 2) mapping of neuronal mechanisms involved in sensory integration, 3) the role of early viral brain infections in the development of sensorimotor function, and 4) the role of nitric oxide in the pharmacological effects of phencyclidine (a drug that produces psychotic symptoms in humans) in pre-attentive information processing and models that reflect higher order of cognitive processing, such as non-associative and associative learning as well as working memory.


Working Model



SELECTED RECENT PUBLICATIONS

  • Engel JA, Enerbäck C, Fahlke C, Hulthe P, Hård E, Johannessen K, Svensson L, Söderpalm B (1992) Serotonergic and dopaminergic involvement in ethanol intake. In: Novel Pharmacological Intervention for Alcoholism (Eds: C A Naranjo and E M Sellers), Springer-Verlag, pp 68-92

  • Engel JA, Fahlke C, Hulthe P, Hård E, Johannessen K, Snape B, Svensson L (1988) Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists. J Neural Transmission 74: 181-193

  • Engel JA, Zhang J, Bergstrom T, Conradi N, Forkstam C, Liljeroth A, Svensson L (2000) Neonatal herpes simplex virus type 1 brain infection affects the development of sensorimotor gating in rats. Brain Res 863: 233-240

  • Larsson A, Engel JA (2004) Neurochemical and behavioral studies on ethanol and nicotine interactions. Neuroscience and Biobehavioral Reviews 27: 713-720

  • Larsson A, Jerlhag E, Svensson L, Söderpalm B, Engel JA (2004) Is an α-conotoxin MII-sensitive mechanism involved in the neurochemical, stimulatory, and rewarding effects of ethanol? Alcohol 34: 239-250

  • Zhang J, Engel JA, Söderpalm B, Svensson L (1998) Repeated administration of amphetamine induces sensitisation to its disruptive effect on prepulse inhibition in the rat. Psychopharmacology (Berl) 135: 401-406

  • Zhang J, Engel JA, Ericson M, Svensson L (1999) Involvement of the medial geniculate body in prepulse inhibition of acoustic startle. Psychopharmacology (Berl) 141: 189-196

  • Pålsson E, Klamer D, Wass C, Archer T, Engel JA, Svensson L. (2005) The effects of Phencyclidine on Latent Inhibition in Taste Aversion Conditioning: Differential Effects of Preexposure and Conditioning. Behavioural Brain Research 157(1): 139-46

  • Klamer D, Zhang J, Engel JA, Svensson L (2005) Selective interaction of nitric oxide synthase inhibition with phencyclidine: Behavioral and NMDA-receptor binding studies in the rat. Behavioural Brain Research 159(1): 95-103

  • Klamer D, Pålsson E, Fejgin K, Zhang J, Engel JA, Svensson L (2005) Activation of a nitric oxide sensitive cAMP pathway with phencyclidine: elevated hippocampal cAMP levels are temporally associated with deficits in prepulse inhibition. Psychopharmacology (Berl) 179(2): 479-88


    MAJOR FUND PROVIDERS

  • Stanley Foundation Research Programs

  • The Swedish Research Council

  • The Swedish Labour Market Insurance (AFA)

  • Research Projects Financed by Grants from the State under the LUA agreement (LUA)