Abstract
Cocaine addiction is an acquired behavioral state developed in vulnerable individuals after cocaine exposure. It is characterized by compulsive drug-seeking and high vulnerability to relapse even after prolonged abstinence, associated with decreased neurogenesis in the hippocampus. This addictive state is hypothesized to be a form of “memory disease” in which the drug exploits the physiological neuroplasticity mechanisms that mediate regular learning and memory processes. Therefore, a major focus of the field has been to identify the cocaine-induced neuroadaptations occurring in the usurped brain’s reward circuit. The neurosteroid dehydroepiandrosterone (DHEA) affects brain cell morphology, differentiation, neurotransmission, and memory. It also reduces drug-seeking behavior in an animal model of cocaine self-administration. Here, we examined the long-lasting effects of DHEA treatment on the attenuation of cocaine-seeking behavior. We also examined its short- and long-term influence on hippocampal cells architecture (neurons and astrocytes). Using a behavioral examination, immunohistochemical staining, and diffusion tensor imaging, we found an immediate effect on tissue density and activation of astrocytes, which has a continuous beneficial effect on neurogenesis and tissue organization. This research emphasizes the requites concert between astrocytes and neurons in the rehabilitation from addiction behavior. Thus, DHEA may serve as a treatment that corrects brain damage following exposure to and abstinence from cocaine.
Highlights
Drug addiction is a complex disease involving mind and body, defined as the compulsion to consume a drug while losing control over the amount consumed (Everitt et al, 2001)
The results show a significant effect of DHEA treatment on tissue directionality and organization in the DTI2 fractional anisotropy (FA) parameter (Supplementary Figure 2B) between the COC-SAL and COCDHEA groups)
This study aimed to examine the long-term beneficial effect of DHEA treatment on cocaine addiction
Summary
Drug addiction is a complex disease involving mind and body, defined as the compulsion to consume a drug while losing control over the amount consumed (Everitt et al, 2001). Cocaine usage disorder is characterized by a high propensity for repeated drug use and addictive substance relapse, which can occur during short periods of withdrawal or even following years of successful. The two main challenges associated with treating cocaine dependence are treatment retention and relapse (Penberthy et al, 2010). Merging reports emphasize the importance of both the glutamatergic signaling-pathway and the learning and memory circuit for switching from substance use- to substance abuse-behavior (Doyle et al, 2014). Ample evidence shows neurogenesis reduction in response to various addictive drugs, such as cocaine (Sudai et al, 2011), alcohol (Herrera et al, 2003), opiates (Teuchert-Noodt et al, 2000), and amphetamines (Eisch et al, 2000; Domínguez-Escribà et al, 2006; Eisch and Harburg, 2006). Preventing neurogenesis prior to drug exposure increases susceptibility to drug-seeking behavior (Noonan et al, 2010)
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