Role of dorsomedial striatum neuronal ensembles in incubation of methamphetamine craving after voluntary abstinence

Abstract 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

Distinct fos-expressing neuronal ensembles in the ventromedial prefrontal cortex mediate food reward and extinction memories

In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in “neuronal ensembles.” Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration.Wefirst trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area

Sex Differences in Substance Use and Misuse: A Toxicology Investigators\u27 Consortium (ToxIC) Registry Analysis

Background: Variations between male and female populations are previously reported in classes of harmfully used/misused drugs, severity of substance use disorder and risk of relapse. The aim of this study was to provide a review of bedside medical toxicologist managed, sex-specific poisonings in adults that present with harmful drug use/misuse. Methods: ToxIC Registry cases \u3e /=19 and \u3c /=65 years old, with harmful drug use or misuse during the timeframe June 2010-December 2016, were studied. Demographics, primary agents of toxic exposure, administration route and complications were analyzed. Descriptive methods were used in the analysis. Results: The database included 51,440 cases. Of these, 3426 cases were analyzed in which the primary reason for the encounter was harmful substance use/misuse. Females were found to harmfully use/misuse pharmaceutical drugs (N=806, 65.6%) more than nonpharmaceutical drugs (N=423, 34.4%). Males more frequently used nonpharmaceutical drugs (N=1189, 54.1%) than pharmaceutical drugs (1008, 45.9%). Analgesics were used by females (N= 215, 18.2%) and males (N=137, 6.6%). Sedative hypnotics were used by females (N=165, 14%) and males (N=160, 7.8%). Psychoactive agents were used by males (N=325, 15.8%) and females (N=67, 5.7%). Sympathomimetics were used by males (N=381, 18.5%) and females (N=151, 12.8%). The majority of both male and female participants, 1712 (57.9%), utilized an oral route of administration. However, 312 (16.5%) of males utilized inhalation vs 73 (6.8%) of females inhaled their substance. Conclusion: There were sex-specific differences among patients evaluated for harmful substance use/misuse by toxicologists. Considering these differences in regards to management and preventive approaches may be indicated

Protocol for Monitoring Aquatic Invertebrates of Small Streams in the Heartland Inventory & Monitoring Network, Version 2.1

Executive Summary The Heartland Inventory and Monitoring Network (HTLN) is a component of the National Park Service’s (NPS) strategy to improve park management through greater reliance on scientific information. The purposes of this program are to design and implement long-term ecological monitoring and provide information for park managers to evaluate the integrity of park ecosystems and better understand ecosystem processes. Concerns over declining surface water quality have led to the development of various monitoring approaches to assess stream water quality. Freshwater streams in network parks are threatened by numerous stressors, most of which originate outside park boundaries. Stream condition and ecosystem health are dependent on processes occurring in the entire watershed as well as riparian and floodplain areas; therefore, they cannot be manipulated independently of this interrelationship. Land use activities—such as timber management, landfills, grazing, confined animal feeding operations, urbanization, stream channelization, removal of riparian vegetation and gravel, and mineral and metals mining—threaten stream quality. Accordingly, the framework for this aquatic monitoring is directed towards maintaining the ecological integrity of the streams in those parks. Invertebrates are an important tool for understanding and detecting changes in ecosystem integrity, and they can be used to reflect cumulative impacts that cannot otherwise be detected through traditional water quality monitoring. The broad diversity of invertebrate species occurring in aquatic systems similarly demonstrates a broad range of responses to different environmental stressors. Benthic invertebrates are sensitive to the wide variety of impacts that influence Ozark streams. Benthic invertebrate community structure can be quantified to reflect stream integrity in several ways, including the absence of pollution sensitive taxa, dominance by a particular taxon combined with low overall taxa richness, or appreciable shifts in community composition relative to reference condition. Furthermore, changes in the diversity and community structure of benthic invertebrates are relatively simple to communicate to resource managers and the public. To assess the natural and anthropogenic processes influencing invertebrate communities, this protocol has been designed to incorporate the spatial relationship of benthic invertebrates with their local habitat including substrate size and embeddedness, and water quality parameters (temperature, dissolved oxygen, pH, specific conductance, and turbidity). Rigid quality control and quality assurance are used to ensure maximum data integrity. Detailed standard operating procedures (SOPs) and supporting information are associated with this protocol

Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. Findings We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk. Interpretation Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID