Our research topics are focused on the primary aim of understanding the neurochemical basis of behavior. We use a variety of biomedical methods ranging from optogenetics and electrophysiology through histological techniques to behavioral animal models, chemogenetics and, of course, pharmacological tools.
In the past years, we at Korpi lab have focused on the long-term effects of the GABAA receptor modulating drugs on the dopamine neurons of the ventral tegmental area, or VTA, and on other drugs that might counteract the effects of the drugs of abuse.
We have found that single ex vivo exposures to addictive, dependence-causing, synaptically active benzodiazepines, diazepam and zolpidem, and to two non-benzodiazepines, extrasynaptically active gaboxadol and ganaxolone, induce glutamate receptor neuroadaptation in mouse VTA dopamine neurons. This process involves cellular plasticity and represents long-lasting neuroadaptation of the glutamatergic system in the VTA through, at the systems level, disinhibition of DA neurons.
Interestingly, these latter drugs do not show rewarding properties in mice or baboons, but induce conditioned place aversion in mice. This result fits with a dichotomous functional/structural organization of VTA dopamine neuron populations in monkeys and mice.
We have also found interesting anti-addictive effects of pregabalin (a presynaptic Ca2+ channel downregulator) and rac-BHFF (a GABAB receptor positive allosteric modulator) on VTA neuroplasticity and behaviours induced by drugs of abuse.
The current projects of the lab, aiming to elaborate the neuronal circuits behind the addictive behaviours, are described below.
We have recently reviewed the regulation and neuroplasticity of midbrain neurons as the critical part of reward/aversion circuitry for a number of drugs of abuse, and found that the idea of diverse populations of VTA dopamine and GABA neurons is still waiting for more detailed neurobiological and behavioural assessment and verification.
- To establish the cellular heterogeneity and circuitry in the mouse midbrain, with the focus on the ventral tegmental area.
- To link the VTA cellular subtypes to rewarding, emotional and/or cognitive behaviours.
Main researchers: E. Nagaeva, E. Korpi
Funded by: Academy of Finland
Serotonin is thought to play a part in formation of addictive behavior. This has been interestingly reflected in clinical studies, conducted in between 1950's and 1970's and again more recently, showing that nonselective serotonin receptor agonists, psychedelics lysergic acid diethylamide (LSD) and psilocybin can reduce alcohol drinking.
In this new project we aim to elucidate the biological mechanisms behind these clinically shown effects.
- To establish the back-translateability of the earlier clinical findings.
- To elucidate the biological mechanism by which the serotonin agonists modulate the circuitries involved in addicition.