Office: (301) 443-7695

Lab: (301) 443-3769

Fax: (301) 480-0466

E-mail: alvarezva@mail.nih.gov

 We are interested in understanding the morphological and functional changes that take place at synapses during acute exposure to drugs of abuse and as a consequence of chronic treatment with them. It is currently believed that a person or research animal “learns how to beome addicted” with repetitive exposures to drug and that addictive behaviors share common features with models of learning. Then, a reasonable hypothesis has been that at a cellular level, addiction makes use of similar mechanisms as learning. Indeed, addictive substances, such as cocaine and alcohol, induce long-term changes in synaptic strength in areas of the brain involved in reward-related learning (e.g. the nucleus accumbens). Now, exactly what are all these changes in synaptic function, what signaling pathways are involved and what are the consequence to the excitability and output of the neurons affected are questions that need detailed answers.

In addition, evidences exists that prolong exposure to cocaine and amphetamines produces long-lasting changes in neuronal morphology and increases the density of dendritic spine in neurons of the nucleus accumbens and prefrontal cortex. Because the location and density of dendritic spines can predict those of the glutamatergic synapses in many regions of the brain, we propose that these morphological changes reflect changes in neuronal connectivity. The increases in spine density are long-lived (as they are seen more than 1 month after last administration) and they suggest that drug-induced structural plasticity might play a role in the long lasting behavioral abnormalities that characterize addiction.  Many important questions remain unanswered with respect to the structural plasticity and its significance.

The laboratory uses a combination of techniques including electrophysiology to record synaptic responses and 2-photon laser scanning microscopy to measure calcium signals in spines and image synaptic morphology simultaneously. Two-photon uncaging of caged neurotransmitters and peptides as well as biochemistry are other techniques applied in order to understand the role of neurotransmitters, signaling molecules, and of the actin cytoskeleton in the regulation of spine structure and synaptic function. Our main goal is to better understand the changes that occur when animals are exposed and become addicted to alcohol and other drugs of abuse. 

 Lab Members

Gail Seabold, PhD

Postdoctoral Fellow

seaboldg@mail.nih.gov

(start day: August 1, 2008)

Alice Dobi (Yue Wu), PhD

Postdoctoral Fellow

wuyue2@intra.nida.nih.gov

(start day: June 1, 2008)

Roland Bock, MSc

Lab Technician

bockr2@mail.nih.gov

Elizabeth Kirby

Lab Secretary

kirbye@mail.nih.gov