Dataset Information

Escalated Oxycodone Self-Administration Causes Differential Striatal mRNA Expression of FGFs and IEGs Following Abstinence-Associated Incubation of Oxycodone Craving.

ABSTRACT: Addiction to prescribed opioids including oxycodone has reached tragic levels. Herein, we investigated the relevance of fibroblast growth factors (FGFs) and immediate early genes (IEGs) to withdrawal-induced incubation of drug craving following escalated oxycodone self-administration (SA). Rats were trained to self-administer oxycodone for 4?weeks. Seeking tests were performed at various intervals during 1 month of drug withdrawal. Rats were euthanized 1 day after the last test and nucleus accumbens and dorsal striata were dissected for use in PCR analyses. Rats given long access (LgA, 9?h), but not short access (ShA, 3?h) to drug escalated their oxycodone intake and exhibited incubation of oxycodone seeking during withdrawal. These rats exhibited dose-dependent increases in fgf2 expression in the dorsal striatum. Fgfr2 expression was also significantly increased in the striatum in LgA, but not ShA groups. Similarly, striatal c-fos and junB mRNA levels showed greater increases in LgA rats. The observations that fgf mRNA levels were more altered in the dorsal striatum than in the NAc of LgA rats suggest that changes in striatal FGF expression may be more salient to incubation of oxycodone craving than alterations in the NAc. Targeting FGF signaling pathways might offer novel strategies against opioid addiction.

SUBMITTER: Blackwood CA

PROVIDER: S-EPMC7448685 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Escalated Oxycodone Self-Administration Causes Differential Striatal mRNA Expression of FGFs and IEGs Following Abstinence-Associated Incubation of Oxycodone Craving.

Blackwood Christopher A CA Leary Michael M Salisbury Aaron A McCoy Michael T MT Cadet Jean Lud JL

Neuroscience 20190724

Addiction to prescribed opioids including oxycodone has reached tragic levels. Herein, we investigated the relevance of fibroblast growth factors (FGFs) and immediate early genes (IEGs) to withdrawal-induced incubation of drug craving following escalated oxycodone self-administration (SA). Rats were trained to self-administer oxycodone for 4 weeks. Seeking tests were performed at various intervals during 1 month of drug withdrawal. Rats were euthanized 1 day after the last test and nucleus accum ...[more]

PMID: 31351142

Similar Datasets

Project description:We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d. We used in situ hybridization to measure the colabeling of the activity marker Fos with Drd1 and Drd2 in DMS and DLS after the tests. Based on the in situ hybridization colabeling results, we tested the causal role of DMS D1 and D2 family receptors, and DMS neuronal ensembles in "incubated" methamphetamine seeking, using selective dopamine receptor antagonists (SCH39166 or raclopride) and the Daun02 chemogenetic inactivation procedure, respectively. Methamphetamine seeking was higher after 21 d of voluntary abstinence than after 1 d (incubation of methamphetamine craving). The incubated response was associated with increased Fos expression in DMS but not in DLS; Fos was colabeled with both Drd1 and Drd2 DMS injections of SCH39166 or raclopride selectively decreased methamphetamine seeking after 21 abstinence days. In Fos-lacZ transgenic rats, selective inactivation of relapse test-activated Fos neurons in DMS on abstinence day 18 decreased incubated methamphetamine seeking on day 21. Results demonstrate a role of DMS dopamine D1 and D2 receptors in the incubation of methamphetamine craving after voluntary abstinence and that DMS neuronal ensembles mediate this incubation. SIGNIFICANCE STATEMENT:In human addicts, abstinence is often self-imposed and relapse can be triggered by exposure to drug-associated cues that induce drug craving. We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we used classical pharmacology, in situ hybridization, immunohistochemistry, and the Daun02 inactivation procedure to demonstrate a critical role of dorsomedial striatum neuronal ensembles in this new form of incubation of drug craving.

Dataset Information

Escalated Oxycodone Self-Administration Causes Differential Striatal mRNA Expression of FGFs and IEGs Following Abstinence-Associated Incubation of Oxycodone Craving.

Publications

Escalated Oxycodone Self-Administration Causes Differential Striatal mRNA Expression of FGFs and IEGs Following Abstinence-Associated Incubation of Oxycodone Craving.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets