Laboratory of Behavioral Pharmacology
Research profile
In the Behavioural Pharmacology Laboratory we conduct behavioural studies on the role of chronic stress in aetiology of neuropsychiatric diseases (depression, treatment-resistant depression, schizophrenia). With the use of a Chronic Mild Stress model of depression, we also do a basic research on identification of new, potential antidepressants and other non-pharmacological (eg. Deep Brain Stimulation) treatments for depression. Finally, we investigate mechanisms of coexistence of anhedonia, anxiety, cognitive disorders, drug addictions and depression in animals.
Research methods
In our behavioural studies we employ Wistar and/or Wistar-Kyoto rats. Our methodology includes the following models and tests:
- Models of depression: Chronic Mild Stress, Forced Swim test, Olfactory Bulbectom, Deep Brain Stimulation and Optogenetic stimulation and inhibition in animal models of treatment-resistant depression
- Models of anxiety: Open Field, Elevated Plus-Maze, Vogel's test, Spontaneous Alternation test
- Models of cognitive deficits: Novel Object Recognition, Delayed Spatial Alternation test
- Brain reward system: Sucrose consumption test, Conditioned Place Preference and Aversion
- Dependence and drug abuse: measures of physical and psychological dependence, precipitated and conditioned withdrawal effects, withdrawal- and cue-induced place aversions
The most important recent discoveries
- Demonstrating that, in the CMS model of depression, repeated administration of compounds with different pharmacological profiles cause effects similar to those observed after traditional antidepressants, with significant faster onset of action. Two of the compounds tested in this procedure, (agomelatine, escitalopram), are now officially registered and used to treat depression in humans, and the next few ones are in the clinical trial phase.
- Demonstration that repeated administrations of rivastigmine, donepezil and ketamine, but not memantine, reverse the CMS-induced anhedonia, anxiety and cognitive deficits.Demonstration that the CMS procedure causes impairments similar to those observed obsessive-compulsive disease (OCD) in humans. These effects are mediated by the dopaminergic D2 and D3 receptors in the nucleus accumbens septi and are normalized by a repeated administration of SSRIs but not imipramine.
- Demonstration that the CMS procedure accelerates the development of dependence on various addictive substances (morphine, nicotine, diazepam) and enhances physical and motivational withdrawal symptoms in addicted animals. These effects are normalized by repeated administration of SSRIs.
- Demonstration that Deep Brain Stimulation (DBS) in ventro-medial prefrontal cortex reverses the CMS-induced anhedonia, anxiety and cognitive deficits in two animal models of drug-resistant depression, and presenting evidence that these effects are not mediated by the dopaminergic D1, D2 and D3 receptors.
