Department of Molecular Neuropharmacology


Our research focuses on three areas: the reward system of the brain, the molecular mechanisms of drug action, and neuro-pharmacogenomics.

The reward system of the brain encompasses all brain areas involved in reward-driven behaviors, with the mesolimbic dopamine system at the core. We have been studying the mechanisms involved in the plasticity of dopaminergic and dopaminoceptive neurons, and also the role of endogenous opioids in signaling rewards.

As the name of the Department implies a large part of our research focuses on the cellular and the molecular mechanisms of actions of psychotropic drugs, also with an emphasis on opioids. We hope that elucidating molecular signatures of drug action will lead to the identification of mechanisms essential for their therapeutic effects.

In recent years we have also been involved in neuro-pharmacogenomics, searching for associations between genetic background, neuropsychiatric disorders, and the effectiveness of pharmacotherapy. We use next-generation sequencing to discover novel common as well as rare genetic variants associated with drug effectiveness and safety. This is of particular interest in psychiatry due to large interindividual differences in therapy responses.



More publications
  • Kappa opioid receptors integrate neuronal signaling involved in social behavior, Jan Manuel Rodriguez Parkitna, PhD
    National Science Centre grant OPUS
    Beneficial interactions with other members of the same species are an essential part of normal behavior. Social interactions engage multiple neuronal pathways, but as evidence shows their rewarding effects converge in the brain’s reward system. We hypothesize that signaling through kappa opioid receptors in the nucleus accumbens (NAc) plays a key role in this process, and enables normal social behaviors. Specifically, we propose that dynorphin activates kappa opioid receptors located in the NAc presynpatically on oxytocin, dopaminergic and serotonergic neurons. Therefore, dynorphin release triggered by any of the above three neurotransmitters would lead to local inhibition of all three of them. The goal of this project is to test this hypothesis, and thus confirm a mechanism through which kappa opioid receptors in the NAc control social behaviors. To prove the hypothesis we will generate genetically modified mice with selective inactivation of kappa opioid receptors in dopaminergic, serotonergic or oxytocin neurons. We expect that these mutations should enhance rewarding effects of social contact, and block the effects of nalmefene (a partial agonist of kappa opioid receptors) on social conditioned place preference. To confirm that signaling in the NAc is responsible for the observed phenotypes, we will generate mice with deletion of kappa opioid receptors in neurons projecting to the NAc (using rAAV2-Cre). We will also test the phenotype of mice with deletion of the gene encoding the precursors of dynorphins, as it should replicate most of the phenotypes observed with the selective mutations. The major outcome of the project will be the demonstration of a mechanism involved in mediating social reward. This should offer insight into mechanisms that may underlie psychopathologies that are associated with social impairments and a potential target for treatment. Furthermore, a dynorphin-mediated interaction between dopamine and serotonin signaling could be involved in all forms of reward-driven behaviors.
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  • The Jerzy Konorski Team Award for the best study in neurobiology conducted in Poland awarded every year by the Polish Neuroscience Society and Committee of Neurobiology of the Polish Academy of Sciences, Jan Manuel Rodriguez Parkitna, PhD
    Friday, 1 January 2010
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