Increased Excitability of Lateral Habenula Neurons in Adolescent Rats following Cocaine Self-Administration
Year: 2014
Type: article
Abstract: BACKGROUND: The lateral habenula is a brain region that has been critically implicated in modulating negative emotional states and responses to aversive stimuli. Exposure to addictive drugs such as cocaine negatively impacts affective states, an effect persisting longer than acute drug effects. However, the mechanisms of this effect are poorly understood. We hypothesized that drugs of abuse, such as cocaine, may contribute to drug-induced negative affective states by altering the firing properties of lateral habenula neurons, thus changing the signaling patterns from the lateral habenula to downstream circuits. METHODS: Using whole-cell current-clamp recording of acutely prepared brain slices of rats after various periods of withdrawal from cocaine self-administration, we characterized an important heterogeneous subregion of the lateral habenula based on membrane properties. RESULTS: We found two major relevant neuronal subtypes: burst firing neurons and regular spiking neurons. We also found that lateral habenula regular spiking neurons had higher membrane excitability for at least 7 days following cocaine self-administration, likely due to a greater membrane resistance. Both the increase in lateral habenula excitability and membrane resistance returned to baseline when tested after a more prolonged period of 45 days of withdrawal. CONCLUSION: This is the first study to look at intrinsic lateral habenula neuron properties following cocaine exposure beyond acute drug effects. These results may help to explain how cocaine and other drugs negatively impact affect states.
DOI: 10.1093/ijnp/pyu109
Authors: P. A. Neumann, M. Ishikawa, M. Otaka, Y. H. Huang, O. M. Schluter, Y. Dong
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,693
Awards: Homeostatic Plasticity in Nucleus Accumbens, Cocaine-induced Adaptation in NMDA receptors, Training Program in the Neurobiology of Substance Use and Abuse, Synaptic Reorganization in Drug Addiction, G7487498766, G8368836224, Homeostatic Regulation and Dysregulation in Cocaine Craving, G8418633514, Cocaine-induced adaptation in NMDA receptors
OpenAlex ID: W2145068726