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RESEARCH AREAS

Experience-Dependent Plasticity in Addiction and Mood Disorders

Our research examines how genetic predisposition interacts with experience-dependent plasticity to shape vulnerability to addiction and mood-related conditions. We focus on the CACNA1C and CACNA1D genes, top risk candidates for neuropsychiatric and substance use disorders. These genes encode L-type calcium channels CaV1.2 and CaV1.3, respectively, which are key players in how neurons adapt to experiences. By studying how these channels regulate dopamine and glutamate signaling in brain circuits controlling reward, emotion, and motivation, we seek to connect genetic and molecular mechanisms to behavioral outcomes, revealing how calcium signaling contributes to the brain’s adaptive and maladaptive responses to drugs and stress.

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Relevant Articles

Kabir et al. (2017)

Kabir, Martinez-Rivera, Rajadhyaksha (2017)

Bavley et al. (2020)

Burgdorf et al. (2020)​​

Endocannabinoid–Opioid Interactions in Addiction

Our research explores how the endocannabinoid (eCB) and opioid systems interact to shape the behavioral and neural effects of opioids. We focus on monoacylglycerol lipase (MAGL), the principal enzyme regulating the endogenous cannabinoid 2-AG, to determine how its inhibition alters opioid responses.

Using behavioral mouse models combined with circuit-specific approaches to assess brain activity, neurotransmitter dynamics, and molecular mechanisms, we aim to uncover how MAGL inhibition influences opioid reward, withdrawal, and analgesia. Our goal is to identify eCB-targeted strategies that mitigate opioid dependence and relapse risk while preserving therapeutic pain relief.

Relevant Articles

Martinez-Rivera et al. (2024)

Our Models, Tools & Techniques

In the Rajadhyaksha Laboratory, we employ a variety of neuroscience techniques. By integrating different sets of techniques and models, we can tackle emerging research questions.

  • Animal models of substance use disorders

  • Animal models of mood-related disorders

  • Behavioral assays

  • Genetic manipulations to induce cell-specific targeting

  • Viral approaches to dissect specific neurocircuits

  • Molecular biology techniques

  • In vivo fiber photometry with calcium indicators and neurotransmitter biosensors

Neuroanatomy, molecular pathways & behavior involving CaV1.2 and CaV1.3 (From Kabir, Martinez-Rivera & Rajadhyaksha, 2017)

2-AG Project Schematics 251123.tiff

Inhibiting MAGL-mediated 2-AG degradation elevates 2-AG levels, attenuating opioid responses.

CaV1.2 & CaV1.3 in Brain.jpg
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