Contact Information

Group leader:

Petri Hyytiä
Ph.D., docent
Tel: +358-2941 25334
Fax: +358-2941 25302
Email: petri.hyytia [at] helsinki.fi

Street address:
Haartmaninkatu 8
(Biomedicum Helsinki)
00290 Helsinki

Mailing address:
P.O. Box 63
00014 University of Helsinki
Finland

 

Neuroimaging in Animal Models of Addiction

Several hypotheses have been presented to explain the neuropsychological and neurobiological basis of the compulsive and inflexible consumption of abused drugs. According to these hypotheses, the occurrence of compulsive drug use could reflect the establishment of automatic stimulus‐response habits, drug‐induced loss of impulse control, sensitization of incentive motivation system, or dysregulation of hedonic homeostasis. In spite of the elaborated theoretical framework, the progression from controlled to compulsive drug use remains poorly understood both at the behavioural, neural systems, and molecular level.

In humans and nonhuman primates, neuroimaging techniques have helped to unravel the neurobiological basis of addiction. These techniques have been used for mapping the brain circuits mediating the acute effects of drugs and various stimuli associated with them, as well as the interaction of drugs with specific protein targets in the brain. In contrast, such investigations have generally not been possible in rodents.

Manganese‐enhanced Magnetic Resonance Imaging(MEMRI) is now emerging as a promising method for functional brain imaging in non‐restrained rodents. Metal manganese, in the form of its divalent ion, Mn2+, is paramagnetic. In the CNS, Mn2+ can enter excitable cells via Ca2+ transport mechanisms, including voltage‐gated Ca2+ channels and the Na+/ Ca2+ exchanger. Once in cells, some Mn2+ is transported anterogradely in axons to terminals, and released into the synaptic cleft, from which is can be taken up by other neurons. Therefore accumulation of Mn2+ inside neurons and the surrounding tissue is proportional to neural activity. Because the divalent Mn2+ is paramagnetic and reduces the longitudinal relaxation times (T1) of water protons, it is possible to see enhanced signal intensity of T1‐weighted MR images at the locations where Mn2+ accumulates.

The properties of manganese make it a particularly useful contrast agent for several applications. For example, the ability of Mn2+ to enter excitable cells can be used for mapping active brain regions. This property of MEMRI can be used for assessment of functional connectivity in the brain, defined as temporally correlated activity across functionally related areas. Furthermore, because the efflux of Mn2+ from the brain is slow, the pattern of Mn2+ accumulation is retained for long times. Therefore MEMRI can be performed after behavioural testing that can involve complex behaviours in various environments.

We are currently assessing the alterations in brain reinforcement pathways induced by long-term alcohol drinking using the alcohol‐preferring AA (Alko Alcoholic) rat line, which is one of the best characterized animal models of excessive alcohol consumption. These rats have been extensively characterized for their behavioural and neurochemical traits, yet the neural substrates underlying high alcohol drinking remain elusive. In addition, our goal is to test pharmacological agents that could reverse the disruptions in functional connectivity observed in animals with a history of chronic drinking. These agents will be medications approved for treating alcoholism or novel pharmacological agents in early stages of development.

Collaboration

  • Animal MRI imaging is conducted with close collaboration with the Helsinki Biomedicum Imaging Unit (Dr. Turgut Tatlisumak, Dr. Usama Abo-Ramadan).
  • Our group is a member of the TRANSALC consortium:  “Translational Neuroimaging in Alcoholism: Identification of Altered Brain Connectivity and Treatment Efficacy Predictors”. The project started in March 2011 under a joint funding scheme implemented by ERA-NET NEURON and is funded by the Academy of Finland.
  • Our group is part of the NeuroMedUH research consortium at the Institute of Biomedicine