PRINCIPAL INVESTIGATORS

Marisela Morales, M.S., Ph.D., Senior Investigator

Chief, Neuronal Networks Section

Post-doctoral training - University of Colorado, Boulder, CO (advisor: Dr. Eva Fifková). The Scripps Research Institute, La Jolla, CA (advisor: Dr. Floyd Bloom).

Ph. D. - Biochemistry and Cell Biology. Universidad de Guanajuato, Institute of Experimental Biology (IIBE), Mexico.

M.S. - Biochemistry and Cell Biology. Universidad de Guanajuato, Institute of Experimental Biology (IIBE), Mexico.

B.S. - Biochemistry and Microbiology. Instituto Politecnico Nacional (IPN), School of Biological Sciences. Mexico.

RESEARCH INTERESTS

We are investigating the molecules, cells and neuronal pathways central to the neurobiology of drug addiction. Towards this end, we apply anatomical, cell molecular, cell biological and electrophysiological experimental approaches. Our research focus on two issues: what is the brain circuitry through which addictive drugs have their habit-forming actions, and what are the neuroadaptations in this circuitry that accompany the transition from recreational to compulsive drug-taking?

Accumulating evidence indicate that the ventral tegmental area (VTA) plays a role in goal-directed behavior and in reward processing to natural rewards and to several drugs of abuse. Therefore, we are investigating the neuronal properties and synaptic connectivity of the VTA to gain a better understanding of the interactions of the VTA with other brain structures in the processing and integration of information underlying behaviors associated with the neurobiology of drugs of addiction. Two populations of VTA neurons, dopaminergic neurons and GABAergic neurons, have been extensively characterized. Unexpectedly our work has recently shown that glutamatergic neurons are also present in the VTA. We are currently exploring the neuronal connectivity of VTA glutamatergic neurons and their participation in animal behavior.

Clinical observations and results from animal models indicate that behaviors associated with intake of drugs of abuse are affected by stress. The neuronal pathways, neurons, and neurotransmitters that mediate interactions between stress and drugs of abuse are not well characterized. In this regard, work from our laboratory has provided evidence indicating synaptic connectivity between the reward and the stress systems at the level of the VTA.

Selected Publications:

1. Dobi A., Elyssa B. Margolis, Hui-Ling Wang, Brandon K.H. and Morales M. (in press). Glutamatergic and non glutamatergic neurons of the ventral tegmental area establish synaptic contacts on local dopaminergic or non-dopaminergic neurons. Journal of Neuroscience.

2. Wang H.L. and Morales M. (2009). Cholinergic neurons of the rat mesopontine tegmentum lack either glutamatergic or GABAergic phenotypes. The European Journal of Neuroscience, 29, 340-358.

3. Wang H.L. and Morales M. (2008). Corticotropin-releasing factor binding protein within the ventral tegmental area is expressed in a subset of dopaminergic neurons. Journal Comparative Neurology, 509,302-318.

4. Tagliaferro P. and Morales M. (2008). Synapses between corticotropin-releasing factor-containing axon terminals and dopaminergic neurons in the ventral tegmental area are predominantly glutamatergic. Journal Comparative Neurology, 506, 616-626.

5. Morales M., Hein K. and Vogel Z. (2008). Hippocampal interneurons co-express transcripts encoding the alpha7 nicotinic receptor subunit and the cannabinoid receptor 1. Neuroscience 152, 70-81.

6. Yamaguchi T., Sheen W. and Morales M. (2007). Glutamatergic neurons are present in the rat ventral tegmental area. The European Journal of Neuroscience, 25,106-118.

7. Shepard J.D., Chung D.T., Shaham Y. and Morales M. (2006). Effect of methamphetamine self-administration on tyrosine hydroxylase and dopamine transporter levels in mesolimbic and nigrostriatal dopamine pathways of the rat. Psychopharmacology (Berl), 185, 505-513.

8. Morales M., Wang S.D., Diaz-Ruiz O. and Hyun-Jin Jho D. (2004). Cannabinoid CB1 receptor and serotonin 3 receptor subunit A (5-HT3A) are co-expressed in GABA neurons in the rat telencephalon. The Journal of Comparative Neurology, 468, 205-216.

9. Morales M. and S.D. Wang (2002). Differential composition of 5-hydroxytryptamine3 receptors synthesized in the rat CNS and peripheral nervous system. The Journal of Neuroscience, 22, 6732-6741.

10. Sarabi A., Hoffer B.J., Olson L. and Morales M. (2001). GFRalpha-1 mRNA in dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area. The Journal of Comparative Neurology, 441, 106-117.