Dr. Reichel is currently an Assistant Professor of Neuroscience at the Medical University of South Carolina. She joined MUSC as a post-doctoral scholar in 2009 and has advanced up the academic ladder over the past 10 years.
My research program is concentrated at the intersection of addiction and cognitive function. A main premise of the laboratory is that all factors underlying disordered behavior are crucial to elucidating treatment options. Some common themes studied by my laboratory are identifying and reducing cognitive consequences during drug abstinence by implementing pharmacological and behavioral treatment interventions, the inclusion of sex differences/similarities throughout, and stress reduction. This research focus results from my eclectic experiences as a masters and doctoral student in combination with my past 10 years in the Department of Neuroscience at MUSC as a post-doctoral fellow, research assistant professor, and assistant professor. Listed below are some of the main contributions to science that have come out of my laboratory.
Establishing the underlying mechanisms of methamphetamine-induced deficits in recognition memory
Methamphetamine addiction is a chronic relapsing disorder unique from other drugs due to pronounced cognitive deficits that occur during abstinence. Memory is one cognitive domain that is particularly impaired in both human and animal models. My laboratory has demonstrated that extended access to methamphetamine self-administration causes reliable deficits in object recognition and object/place recognition memory in male and female rats. These tasks engage a unique and specific circuitry encompassing the hippocampus, prefrontal and perirhinal cortices, with the perirhinal cortex mediating recognition of novelty. We have shown that chronic self-administered meth dysregulates glutamate neurotransmission in the perirhinal cortex and that recognition memory can be restored with glutamatergic prodrugs. Recently, we demonstrated that chemogenetic activation of the perirhinal cortex reverses meth induced impairments in recognition memory and prevents relapse in the presence of novel cues. We continue to pursue these issues by studying the underlying physiology, circuitry, and neurobiology of meth-induced deficits in recognition memory. Currently we are using an AAVretro-Cre approach that employs the retrograde-traveling AAVrg-Cre virus and a Cre-dependent AAV-DIO-hM3Dq or hM4Di to activate or inhibit, respectively, our circuits of interest.
Neurobiology of methamphetamine addiction
Worldwide methamphetamine use is increasing at a rapid rate. Understanding the underlying neurobiology specific to meth addiction will enhance efforts to break the chronic relapsing cycle of addiction. The nucleus accumbens is a well-characterized focal point for drug-induced changes in both dopaminergic and glutamatergic signaling mechanisms. However, since meth has a potent dopamine release mechanism, less attention is devoted to changes in glutamatergic neurotransmission following prolonged meth. Glutamatergic projections from the prefrontal cortex to the nucleus accumbens are critical for reinstatement of drug seeking across several drugs and expression of reinstated meth seeking relies on this excitatory neurocircuitry. Repeated activation of this neurocircuit by drugs of abuse, like meth, induces lasting maladaptive changes. My laboratory and others have reported that 6-hr access to contingent meth results in an escalation of drug intake and impaired cognitive sequelae typically associated with changes within the corticostriatal circuitry. Further, we have found postsynaptic adaptations in ionotropic glutamate receptor distribution and function, expressed as a decrease in AMPA/NMDA ratio in the prefrontal cortex. This change was driven by an increase in NMDA receptor currents and an increase in GluN2B surface expression. In the nucleus accumbens, meth decreased the paired-pulse ratio and increased the frequency of spontaneous excitatory postsynaptic currents with no indication of postsynaptic changes.
Oxytocin and relapse to drug seeking
In recent years, oxytocin has become a prime candidate for the treatment of several neuropsychiatric disorders, including addiction. I have shown that systemic and nucleus accumbens microinfusions of oxytocin consistently decrease drug seeking in male and female rats that have self-administered cocaine and methamphetamine. Surprisingly, little is known about the underlying neurobiology by which oxytocin exerts its effects. Receptors are wide spread in brain and expressed on regionally specific cell-types. We have shown that oxytocin normalized cue-induced fos expression within the addiction circuit, and that oxytocin attenuation of cued reinstatement can be blocked through administration of an mGluR2/3 receptor antagonist. A current line of research in my lab is devoted to identifying cell-type specific effects of oxytocin within the addiction circuitry.
Sex differences in motivated behavior
There are marked sex differences in the etiology of drug addiction that can be emulated in animal models of motivated drug taking. For example, women take more drug, transition faster into addiction, and report more difficulty maintaining abstinence relative to men. These differences are believed to result from a complex interplay between biology, environment, socioculture, and development. My laboratory seeks to identify biological mechanisms that contribute to differences/similarities in addiction. We have found that male and female rats escalate drug intake faster and reinstate extinguished lever pressing to a priming injection of drug to a greater degree than males. However, we also find similar reinstatement to methamphetamine, cocaine, and heroin conditioned cues in both males and females. This is interesting because it is generally believed that females respond more to drug conditioned cues. We believe that the neural underpinnings of the behavior are mediated by different mechanisms in males and females, resulting in convergent sex differences. That is, both sexes exert the same response but the neurobiology mediating the behavior is different. This topic is currently under investigation in my laboratory.
Carmela M. Reichel, Ph.D.
Stewart Cox, MS
MD/PhD Graduate Student
Angela Kearns, BS
Jordan Hopkins, MS
2013-2015 Michael D. Scofield, Ph.D.
2013-2015 Jamie Peters, Ph.D.
2014-2016 Kah-Chung Leong, Ph.D.
2015 Linnea Stephens, Ph.D.
2015-2016 Deveesh Mishra, Ph.D.
2015-2016 Aurelien Berheim, Ph.D.
2017-2018 Rachel Weber, Ph.D.