Behavioral Neuroscience and Its Clinical Applications

BASIC SCIENCE RESEARCH

Evidence linking neuronal immediate early genes to enduring forms of neuronal plasticity has heightened interest in their role in mediating behavioral alterations induced by drugs of abuse and other forms of brain stimulation. As these genes are rapidly induced by neuronal stimulation, they represent a mechanism by which drug administration could elicit long-term adaptations in neuronal function that underlie their reinforcing properties. We have focused on one of these immediate early genes, Narp, which clusters AMPA receptors and is expressed selectively in limbic brain regions regulating behavior. A series of studies we have conducted suggest Narp signaling pathways may represent a potential therapeutic target for drug addiction and possibly other motivated behaviors. For example, we have found that Narp knockout mice are deficient in extinction of drug craving. To learn more about molecular mechanisms and circuitry underlying this finding, we are utilizing viral vectors to locally regulate Narp expression in vivo and field recordings to determine how Narp deletion affects learning in brain reward pathways.

TRANSLATIONAL RESEARCH

Electroconvulsive therapy (ECT) is the most effective available therapy for treating depression however little is known about its mechanism of action. Mice genetically engineered to lack key genes which are inducible by electroconvulsive stimulation and which regulate synaptic plasticity may yield clues to how it works. Although ECT is highly effective, it is not without side-effects and so there has been keen interest in developing alternate forms of therapeutic brain stimulation for depression, such as repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation, that are more focal and do not involve anesthesia. Many aspects of these brain stimulating techniques can be efficiently and effectively studied in animal behavioral models. We have begun such to learn how to improve efficacy and decrease adverse effects of these treatments.  

CLINICAL RESEARCH

ECT:  Although ECT is one the oldest and most established treatments in psychiatry, even in recent years we have continued to learn how we can improve its efficacy and decrease cognitive side-effects associated with the treatment such as by using high dose right unilateral treatment and ultrabrief pulsewidth stimulation. Our team is examining several different aspects of ECT delivery to learn how we can affect and improve on these outcome measures.

VOLUNTEERS NEEDED

Deep Transcranial Magnetic Stimulation (dTMS) for Major Depressive Disorder in Adults
If you are between the ages of 22-68, currently suffering from Major Depressive Disorder (MDD), and have been previously unsuccessfully treated with antidepressant medications you may be eligible to participate in a research study on deep Transcranial Magnetic Stimulation (dTMS). This study is being conducted to evaluate the safety and effectiveness of the H-Coil Transcranial Magnetic Stimulation (TMS) in treating depression. Participation involves 47 visits over 18 weeks. There are a total of two weeks for screening visits to determine eligibility. During this time participants will also need to be gradually taken off of medications. Once eligible, there are 16 weeks of the study procedure. Participants will have a 50% chance of receiving real TMS or sham TMS once a day, 5 days per week for 4 consecutive weeks. Participants will then receive the same TMS (real or sham) twice a week for the remaining 12 weeks.  Participant safety will be monitored, and each participant will be asked questions pertaining to their mood and anxiety. In addition, there is a follow-up visit after 12 weeks. There will be compensation for participating in this study. For more information please call 410-614-1732. The principal investigator is Dr. Irving Reti. (IRB Protocol # NA_00021742). More information (PDF)

RECENT PUBLICATIONS

Reti IM and Baraban JM (2000): Sustained increase in Narp protein expression following repeated electroconvulsive seizure. Neuropsychopharmacology. 23: 439-43.

Reti IM, Baraban JM (2003): Opiate withdrawal induces Narp in the extended amygdala, Neuropsychopharmacology. 28:1606-13.

Johnson AW, Crombag HS, Takamiya K, Baraban JM, Holland PC, Huganir RL, Reti IM (2007): A selective role for neuronal activity regulated pentraxin (Narp) in the processing of sensory-specific incentive value. Journal of Neuroscience. 27: 13430-5.

Wachtel LE, Kahng SW, Cascella N, Dhossche DM, Reti IM (2008): Electroconvulsive Therapy for Severe Catatonic Deterioration in an Autistic Girl with Mental Retardation and Self-injury: A Case Report. American Journal of Psychiatry, 165: 329-33.

Reti IM, Crombag HS, Takamiya K, Sutton JM, Guo N, Dinenna ML, Huganir RL, Holland PC, Baraban JM (2008). Narp regulates long-term aversive effects of morphine withdrawal. Behavioral Neuroscience, 122: 760-8.

Crombag HS, Dickson M, Dinenna M, Johnson AW, Perin MS, Holland PC, Baraban JM, Reti IM (2009). Narp deletion blocks extinction of morphine place preference conditioning, Neuropsychopharmacology, 34: 857-66. Epub 2008 June 4.