Current Research
Puberty as a critical period of addiction vulnerability due to functional maturation processes in the endocannabinoid system
A variety of species typically tend to seek out new stimuli during puberty and show increases in consummatory behavior for appetitive rewards such as sex and food, and importantly, this may extend to drugs of abuse as well. A major goal of the present project will be the examination and characterization of the special sensitivity of pubertal rats to alcohol and non-alcoholic sweetened beverages in comparison to adulthood. Moreover, we are interested in the role of the endocannabinoid system in modulating the primary motivational and rewarding properties of appetitive drug and non-drug related stimuli. The project will be mainly based on pharmacological behavioral experiments, in combination with the use of innovative genetic models of enhanced endocannabinoid signaling. Three different operational measures of appetitive reward/reinforcement efficacy will be used: the progressive ratio schedule, the conditioned place preference test, as well as the newly developed paradigm of conditioned odor attenuation of the startle response, a pioneering animal model for the measurement of hedonic emotional states.
Funding: DFG
Impact of the developing endocannabinoid system in rats on the modulatory influence of stress on adolescent ethanol intake
The endocannabinoid (ECB) system plays a key role in determining the reinforcing effects of alcohol and this appears to be especially true for the pubertal period, where the ECB system has been shown to be overactive. Stress is an important factor that is contributing to an individual’s vulnerability to various neuropsychological dysfunctions, including drug abuse. Growing evidence indicates that pubertal organisms react differentially, both physiologically and behaviorally, to a stressor compared to adults, however, the underlying mechanisms have not been clarified. Finally, a close interaction between the ECB system and stress is already well established. With our project we are therefore aiming to shed light on the mechanisms underlying the heightened influence of stress on the initiation of ethanol intake during puberty/adolescence in rats and investigate the developmental impact of different stressors on ECB functioning.
Funding: DFG, FOR 926 (SP9)
Implication of prefrontocortical maturation of endocannabinoid signaling on the development of cognitive and social skills in the adolescent rat
A major aspect in cognitive development is the ability to suppress inappropriate thoughts and actions in favor of goal-directed behaviors, and these necessary impulse control mechanisms appear to mature during adolescence. Additionally, the prefrontal cortex (PFC) may not be as efficient at regulating social and emotional responses during adolescence compared with earlier and later timepoints in life. We are planning to examine the detailed development of cognitive and social abilities during adolescence. One common denominator in many of these developmental processes is the endocannabinoid (ECB) system which undergoes profound developmental changes during puberty. This modulatory system is not only a major player in mediating cognitive processing and neuroplasticity, but is also strongly involved in social behavior. We will therefore examine a possible correlation between cognitive and social development and maturation of the ECB system, as well as the impact of the developing ECB system on neurodevelopmental alterations (e.g myelination) in the PFC. A third section of the project will focus on risks and consequences of exposure to cognitive enhancers during adolescence, as well as their interaction with the ECB system.
Funding: CIMH Award
Modulations of maternal care and adolescent social rejection in rats as a valid animal model for aspects of borderline personality disorder
The major aim of this research project is to establish an animal model with high face and contruct validity towards aspects of the etiology and symptomatology of borderline personality disorder (BPD). This will be accomplished by early modulations of social relationships and social interaction in juvenile and adolescent rats. It is not intended to mimic the complex disorder completely in rodents, we are rather aiming to induce core symptoms of BPD such as emotional regulation, pain sensitivity and impulse control. Experiences of early social neglect and rejection have been indicated as major factors contributing to the emergence of BPD and we are therefore planning to model maternal neglect in juvenile rats, as well as social exclusion in adolescent animals. Additionally, we are going to examine if a combination of both social manipulations might lead to additive effects. The possible lasting consequences of these manipulations on social, emotional and motivational behavior will then be assessed at different time points of life.
Funding: DFG, KFO 256 (AP1) (associated project)
The neurobiology of reward processing for natural and drug reward during aging
Motivational factors and reward processing have a great impact on key symptoms of frailty. Thus, appetite loss, apathy, and exhaustion are a result, at least in part, of altered reward processing in elderly people. Reward processes involve complex behavioral patterns, including appetitive and hedonic activities which all remain essential as we age. However, the interactions of rewards with an aged brain are only poorly understood. The present project is therefore aiming to investigate age-related changes in the reward system and the behavioral consequences. The main focus will be based on the measurement of the development of sensitivity for food reward during aging and also on the influence of the dopaminergic (DA) and endocannabinoid (ECB) system on this process.
Funding: MWK (D12) (until 2010)
Modulations of the developing endocannabinoid system as an experimental approach towards a valid animal model for schizophrenia
Global evidence indicates that pubertal cannabis use acts as a modest risk factor for the emergence of schizophrenia and it is well known that cannabis use and intoxication can produce short-term exacerbation, recurrences as well as an earlier onset of psychotic symptoms. For this project we are aiming to examine the effects of different modulations of the developing endocannabinoid system (pharmacological treatment, AAV-mediated gene transfer etc.) on possible lasting behavioral and molecular alterations with similarities to the disorder
