OBJECTIVES: This study examined the dependence-producing effects of MG using operant-scheduled behaviour in rats and investigated the potential therapeutic effect of MG by comparing effects to buprenorphine in morphine-dependent rats using the same schedule-controlled behavioural task.
METHODS: The effects of acutely administered MG and morphine were determined in rats trained to respond under fixed-ratio (FR) 10 schedule of food reinforcement. Next, the rats were administered MG and morphine twice daily for 14 consecutive days to determine if physiological dependence would develop by examining cessation of drug treatment and following antagonist-precipitated withdrawal. The study then examined the effects of MG substitution to suppress naloxone-precipitated morphine withdrawal effects on scheduled responding.
RESULTS: Acute doses of MG did not produce dose-related decreases on FR schedules of responding compared to morphine. Unlike morphine, MG-treated rats showed no suppression of response rates following cessation of MG treatment. However, withdrawal effects were evident for MG after precipitation by either naloxone or SR141716A (rimonabant), similar to morphine-treated rats. MG in higher doses (10 and 30 mg/kg) attenuated the naloxone-precipitated morphine withdrawal effects while smaller doses of buprenorphine (0.3 and 1.0 mg/kg) were necessary to alleviate these effects.
CONCLUSION: The findings suggest that MG does not induce physiological dependence but can alleviate the physical symptoms associated with morphine withdrawal which represent the desired characteristics of novel pharmacotherapeutic interventions for managing opioid use disorder (OUD).
METHODS: In a nationally representative cross-sectional study, soon-to-be released prisoners in Kyrgyzstan (N=368) and Azerbaijan (N=510) completed standardized health assessment surveys. After identifying correlated variables through bivariate testing, we built multi-group path models with pre-incarceration official and unofficial detention as exogenous variables and pre-incarceration composite HIV risk as an endogenous variable, controlling for potential confounders and estimating indirect effects.
RESULTS: Overall, 463 (51%) prisoners reported at least one detention in the year before incarceration with an average of 1.3 detentions in that period. Unofficial detentions (13%) were less common than official detentions (41%). Optimal model fit was achieved (X (2)=5.83, p=0.44; Goodness of Fit Index (GFI) GFI=0.99; Comparative Fit Index (CFI) CFI=1.00; Root Mean Square Error of Approximation (RMSEA) RMSEA=0.00; PCLOSE=0.98) when unofficial detention had an indirect effect on HIV risk, mediated by drug addiction severity, with more detentions associated with higher addiction severity, which in turn correlated with increased HIV risk. The final model explained 35% of the variance in the outcome. The effect was maintained for both countries, but stronger for Kyrgyzstan. The model also holds for Kyrgyzstan using unique data on within-prison drug injection as the outcome, which was frequent in prisoners there.
CONCLUSIONS: Detention by police is a strong correlate of addiction severity, which mediates its effect on HIV risk behaviour. This pattern suggests that police may target drug users and that such harassment may result in an increase in HIV risk-taking behaviours, primarily because of the continued drug use within prisons. These findings highlight the important negative role that police play in the HIV epidemic response and point to the urgent need for interventions to reduce police harassment, in parallel with interventions to reduce HIV transmission within and outside of prison.