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Research Group
Cellular and Behavioural Neuroscience
Unit Unit Molecular Neurobiology and Neuropathology »

Associated Investigators Technician
Research Fields
The role of substance P in pain, tolerance and dependence mechanisms to opiates

We study the role of SP in tolerance effects, reward and drugs of abuse dependence, using KO animals for the NK1 gene.

We investigate the molecular and behavioural effects of morphine, comparing to cocaine and amphetamine, which also induce addiction and analgesia, and the morphological localization of the areas of the brain involved. We analyse the possible association and / or dissociation of neural basis which mediate the diverse effects of morphine: analgesia, reward, tolerance, dependence, motor behaviour, withdrawal signs.
Besides, we study the neural basis involved in relapse and compulsive drug self-administration behaviour.

Stress is a precipitating factor in causing relapse into drug taking in man and drug self-administration in animals. However, stress responses can be attenuated by substance P receptor antagonist or by genetic disruption of the substance P receptor. Therefore, drugs that antagonize the actions of substance P may be powerful new tools in both the treatment of opiate drugs addiction and the prevention of relapse into drug taking.

Development of cell therapy in the treatment of neurodegenerative disorders: Alzheimer and Parkinson diseases

In November 1998 derivation of the first human embryonic stem (ES) lines was reported, representing a major step forward for basic research and a potential clinical use in humans. ES cell cultivation in vitro and isolation of specific cell types should lead to their use as renewable source of cells for tissue transplantation, cell replacement and gene therapies. Clinical targets for these cell therapies would include neurodegenerative disorders, diabetes, spinal cord injury, hematopoietic repopulation and myocite grafting.

We propose the use of a mouse model to test the usefulness of ES cell therapy in the treatment of Alzheimer and Parkinson diseases. The aim of this project is to drive neuronal differentiation of mouse ES cells towards cholinergic and dopaminergic phenotypes, that will be transplanted in the brain of the Alzheimer and Parkinson diseases mouse models. These cell therapies should lead to the functional recovery of the brain damage and impaired spatial memory.

The development of ES cell therapy in mouse is a major step towards the possibility of applying this technology to the treatment of Alzheimer and Parkinson diseases and other neurodegenerative or demyelinating disorders.

Representative Publications

De Felipe, C. , Herrero, J.F., O´Brien, J.A., Palmer, J.A., Doyle, C.A., Smith, A.J.H., Laird, J.M., Belmonte, C, Cervero, F., Hunt, S.P. " Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. " Nature . 392 , 394 - 397 ( 1998 )

Gadd CA, , Murtra P, De Felipe C, Hunt SP " Neurokinin-1 receptor-expressing neurons in the amygdala modulate morphine reward and anxiety behaviors in the mouse. " J.Neurosci. . 23(23) , 8271 - 8280 ( 2003 )

Bester, H. , De Felipe, C., Hunt, S.P. " The NK1 receptor is essential for the full expression of noxious inhibitory controls in the mouse. " Journal of Neuroscience . 21 , 1039 - 1046 ( 2000 )

Froger N , Gardier AM, Moratalla R, Alberti I, Lena I, Boni C, De Felipe C, Rupniak NM, Hunt SP, Jacquot C, Hamon M, Lanfumey L. " 5-hydroxytryptamine (5-HT)1A autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization. " J Neurosci. . 25 , 8188 - 8197 ( 2001 )

C.A. Doyle, , C. De Felipe, J.A. O´Brien, J.A. Palmer and S.P. Hunt. " The role of substance P in nociception, analgesia and aggression: The molecular Basis of Pain. " Ed J.Wiley, New York. . 1 , 1 - 1 ( 2000 )
Consejo Superior de Investigaciones Científicas
Universidad Miguel Hernández

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