Perceived risk of cocaine use and experience with cocaine: do they cluster within US neighborhoods and cities?

This study investigates whether experience with cocaine and the perception of risk associated with cocaine use might tend to cluster within neighborhoods and cities in the US. Population-based data from six years of the National Household Surveys on Drug Abuse public use files are employed. The alternating logistic regressions model is used to quantify the extent of geographic concentration. Perceptions of the harm associated with cocaine use and actual experience with cocaine tend to cluster within neighborhoods; once within-neighborhood concentration is taken into account, there is little evidence of residual concentration within cities.     

Opioid modulation of the discriminative stimulus effects of cocaine: comparison of µ, kappa and delta agonists in squirrel monkeys discriminating low doses of cocaine

Modulation of the discriminative stimulus effects of cocaine by the μ agonist morphine, the kappa agonist U 50, 488, and the delta agonist BW 373U86 was investigated in squirrel monkeys using a two-lever drug discrimination procedure. Monkeys initially were trained to discriminate intramuscular injections of 0.3 or 0.56mg/kg cocaine from vehicle and subsequently retrained to discriminate a 3- to 5.6-fold lower dose of cocaine (0.1 or 0.18mg/kg). After retraining, dose-response functions for the discriminative stimulus effects of cocaine were shifted to the left and ED(50) values were reduced 2- to 6-fold compared to values obtained with the higher training doses. In drug substitution experiments, morphine (0.03-1.0mg/kg), U 50,488 (0.1-3.0mg/kg) and BW 373U86 (0.001-0.1mg/kg) did not reproduce the discriminative stimulus effects of the low training doses of cocaine, although U 50,488 engendered a majority of responses on the cocaine-associated lever in two of three monkeys. In drug interaction experiments, pretreatment with morphine (0.3mg/kg) potentiated the discriminative stimulus effects of the low training doses of cocaine such that the cocaine dose-response functions were shifted to the left and ED(50) values were reduced 3- to 7-fold. Pretreatment with U 50,488 (0.3mg/kg), on the other hand, attenuated the discriminative stimulus effects of the low training doses of cocaine such that the cocaine dose-response functions were shifted to the right and ED(50) values were increased approximately 4-fold. The cocaine-modulating effects of morphine and U 50,488 in these experiments were qualitatively similar to those observed previously when the monkeys were trained to discriminate higher doses of cocaine. In contrast to the effects of the μ and kappa agonists, pretreatment with BW 373U86 (0.01 or 0.03mg/kg) did not systematically alter the discriminative stimulus effects of cocaine regardless of training dose.     

Rewarding effects of ethanol and cocaine in µ opioid receptor-deficient mice

To investigate the role of mu opioid receptors in the reinforcing effects of psychotropic drugs, the voluntary ethanol intake and ethanol- and cocaine-induced conditioned place preference in mu opioid receptor-deficient mice and their wild-type counterpartners was tested. Moreover, dopamine D1 and D2 receptor binding was measured. It was found that ethanol intake was significantly lower in deficient mice. Conditioned place preference in wild-type animals was induced with 5.0 mg/kg cocaine and this dose was ineffective in the knockouts. In this group conditioned place preference occurred after injection of 10.0 mg/kg cocaine. Cocaine induced a similar increase in locomotor activity in both groups of mice. There was no difference in dopamine D1 receptor binding, whereas dopamine D2 receptor binding was significantly lower in the hippocampus of deficient animals. This suggests that interaction between opioid systems and dopaminergic systems may account for the differences in responding to the drugs.     

Acquisition of cocaine self-administration in male Sprague–Dawley rats: effects of cocaine dose but not initial locomotor response to cocaine

Rationale  

We have previously described a model in which adult outbred male Sprague–Dawley rats are classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on acute cocaine-induced open-field activation. This model revealed important individual differences in cocaine's effects, including that LCRs exhibited greater responding than HCRs on a progressive ratio schedule of cocaine reinforcement. However, no LCR/HCR differences in acquisition of cocaine self-administration (0.25 mg/kg/12 s infusion) were observed under these conditions.     

Postnatal consequences of prenatal cocaine exposure and myocardial apoptosis: does cocaine in utero imperil the adult heart?

Cocaine use is common among pregnant women with a history of substance abuse, and has been shown to cause abnormalities in the heart during fetal and postnatal development. However, mechanisms underlying the detrimental effects of cocaine on the developing heart are not fully understood. In this issue, Bae and Zhang show that prenatal cocaine exposure increases the susceptibility of the postnatal heart to ischemia and reperfusion injury. Their results suggest that myocardial apoptosis induced by cocaine during fetal development may represent one of the mechanisms by which prenatal cocaine exposure exerts its long-term, deleterious consequences on postnatal cardiac function.     

Alzheimer—like phosphorylation of tau and neurofilament induced by cocaine in vivo

目的:研究可卡因导致细胞环素依赖激酶5(CDK5)过度表达与细胞骨架蛋白阿尔采末病样过度磷酸化的关系。方法:大鼠腹腔注射可卡因(20mg·kg(?)·d~_(-1)),采用免疫印迹技术检测tau蛋白和神经细丝的过度磷酸化。结果:腹腔注射可卡因8天和16天后,大鼠海马、皮质和尾壳核的tau蛋白在PHF-1位点的磷酸化和神经细丝磷酸化水平显著增加。在4天未见细胞骨架蛋白磷酸程度的改变。另外,在同样的脑区和相同的时相点,tau蛋白在Tau-1位点的非磷酸化和神经细丝的非磷酸化水平显著降低。然而,未在实验中发现CDK5和p35的过度表达。结论:腹腔注射可卡因可导致大鼠大脑tau和神经细丝的阿尔采末病样过度磷酸化,但这种变化可能与CDK5的过度激活和表达无关。     

Deletion of the GABAA α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking

Rationale

GABA_A receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine.

Objective

We investigated the reinforcing properties of cocaine in GABA_A α2-subunit knockout (KO) mice using an intravenous self-administration procedure.

Methods

α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg).

Results

No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not.

Conclusions

Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking.     

Women's health and use of crack cocaine in context: Structural and ‘everyday’ violence

BackgroundThere is increasing public health evidence that women who use crack cocaine and are street-involved experience significant health problems and are more isolated with regards to accessing harm reduction and other health-related services. Simultaneously, there is growing acknowledgement that structural and ‘everyday’ violence are significant factors influencing the health of women who use illegal drugs. Little research has examined how these social processes play out for women who use crack cocaine.MethodsA critical ethnography informed by the theoretical constructs of structural and everyday violence and intersectionality was undertaken to explore women's use of crack cocaine within an inner-city neighbourhood in Western Canada. Data collection included baseline survey (n = 126), participant observation and field notes, informal interviews (n = 53), and in-depth interviews (n = 13).ResultsBased on thematic and theoretical analysis two interrelated themes were identified that reflected the interrelationships between women's use of crack, poverty, discrimination, racism, gendered relations of power, and legal policies and practices: (a) the context of health care; and (b) the smoking context.ConclusionsStructural inequities and ‘everyday’ violence are perilously damaging for women who use crack. Interventions to reduce these inequities are urgently needed if we are to reduce the significant suffering of women who are street-involved and use crack cocaine.     

Differences in perimenstrual symptoms between cocaine‐abusing and non‐cocaine‐abusing women

Cocaine abuse among women has become a major health problem in the United States, yet there is little information in the literature concerning the effects of this form of substance abuse on a woman's reproductive system. This study of 65 women in residential treatment for cocaine abuse and 65 non‐cocaine‐abusing women was undertaken to determine if there are differences in frequency or severity of perimenstrual symptoms between these two groups of women. Data were collected by questionnaire and included demographics, a substance use history, and the Menstrual Distress Questionnaire developed by Moos. Findings suggested that there are statistically significant differences in frequency and severity of perimenstrual symptoms between the two groups of women.     

Effects of (−)-Phenylephrine on force of contraction in the presence of cocaine and hydrocortisone in cat papillary muscle

Summary The positive inotropic effect of (–)-phenylephrine, in the presence of propranolol, was studied after inhibition of neuronal and extraneuronal uptake in isolated papillary muscles from reserpine-pretreated cats. An inhibition of extraneuronal uptake with hydrocortisone influenced the effect of (–)-phenylephrine neither when present alone nor in the presence of cocaine (additional inhibition of neuronal uptake). An inhibition of neuronal uptake with cocaine caused a small but significant increase in the potency of (–)-phenylephrine. We conclude that in cat ventricular cardiac muscle the extraneuronal compartment is apparently neither a site of loss nor a site of gain for (–)-phenylephrine with respect to force of contraction.     

Differential effects of self-administered cocaine in adolescent and adult rats on stimulus–reward learning

Rationale Adult cocaine addicts, abstinent at the time of testing, show a variety of neurocognitive impairments. Less clear is whether there are differences in the degree of impairment if cocaine use is initiated during adolescence rather than adulthood. Objectives Using a preclinical model, we evaluated if stimulus–reward learning was impacted differently in rats exposed to cocaine during adolescence (beginning on postnatal day 37) vs adulthood (beginning on postnatal days 74–79) and then tested after a drug-free period. Materials and methods A yoked-triad design of intravenous cocaine self-administration in adult (n = 8 triads) and adolescent (n = 8 triads) rats was used. Sets of three animals either contingently self-administered cocaine or received cocaine or saline in a noncontingent manner. Rats self-administering 1-mg/kg doses of cocaine responded under a fixed-ratio 5, timeout 20-s schedule of reinforcement. After 18 2-h drug or saline sessions, all rats (now adults) began the drug-free period in their home environments. Testing in a stimulus–reward learning task (conditioned cue preference) began 19 days later. Results Self-administration behavior was similar in adolescent and adult rats. Lever responses were not significantly different, and both age groups averaged approximately 20 infusions per session. Rats contingently self-administering cocaine or passively exposed to cocaine during adulthood showed stimulus–reward learning deficits in the conditioned cue preference task. Rats exposed to contingent or noncontingent cocaine during adolescence had normal learning, showing strong preferences for a Froot Loops-paired cue. Conclusions These findings suggest that adolescents are insensitive to cocaine-induced impairment of learning related to amygdala memory system functioning.     

Seeking–taking chain schedules of cocaine and sucrose self-administration: effects of reward size,reward omission,and α-flupenthixol

Rationale  

In heterogeneous seeking–taking (ST) chain schedules of self-administration, seeking rewards and taking rewards are distinct actions, giving animals explicit control over their intake of the reward. However, the neurobehavioral characteristics of ST chain schedules are relatively unexplored.     

Lack of involvement ofδ-opioid receptors in mediating the rewarding effects of cocaine

The non-selective opioid antagonist naltrexone and the partial agonist buprenorphine have been reported to reduce cocaine self-administration (SA) and relapse in both humans and rhesus monkeys. Data suggesting an involvement of-opioid receptors in modulating the conditioned rewarding effects of cocaine were also recently presented. In view of such findings, the present SA and place conditioning studies were conducted to examine the influence of the selective-opioid receptor antagonist naltrindole upon the rewarding effects of cocaine. Sprague-Dawley rats were trained to self-administer cocaine (1.0 mg/kg per infusion) on an FR2 schedule of reinforcement. Dose-response and antagonist testing commenced once stable rates of cocaine SA were achieved. For antagonist testing, rats received naltrindole (0.03–10.0 mg/kg, IP) 30 min prior to the start of 2-h SA sessions. SA behavior in response to cocaine delivery (0.25 and 1.0 mg/kg per infusion) was then determined. Naltrindole in doses of 0.03–3.0 mg/kg did not alter the number of cocaine infusions taken by the rats. A higher dose of naltrindole (10.0 mg/kg), which markedly depressed locomotor activity, resulted in a 16% reduction of cocaine (0.25 mg/kg per infusion) SA behavior. When SA sessions were terminated and naltrindole (1.0 mg/kg) was administered repeatedly for 3 days, no alterations in the re-acquisition of cocaine SA were seen. Place conditioning studies also failed to find an effect of naltrindole (0.1–3.0 mg/kg) on cocaine (10 mg/kg) — induced conditioned place preferences. Naltrindole, by itself, did not induce significant place conditioning. These data fail to indicate a role of-opioid receptors in modulating either the positive reinforcing or conditioned rewarding effects of cocaine. Furthermore, they suggest that the therapeutic actions of naloxone, naltrexone and buprenorphine on cocaine SA behavior may not result from the specific blockade of-opioid receptors.     

Euphorigenic doses of cocaine reduce [123I]β-CIT SPECT measures of dopamine transporter availability in human cocaine addicts

The in vivo potency of euphorigenic doses of intravenous cocaine for displacing [¹²³I]-CIT ([¹²³I]2-carbomethoxy-3-(4-iodophenyl)tropane) binding to striatal dopamine transporters (DAT) was assessed in human cocaine addicts using single photon emission computed tomography (SPECT). Cocaine-dependent subjects (n=6) were injected with [¹²³I]-CIT and imaged 24 h later under equilibrium conditions. Sequential cocaine infusions (0.28±0.03 and 0.56±0.07 mg/kg) produced significant (P<0.0005) reductions in the specific to non-specific equilibrium partition coefficient, V₃ (6±6 and 17±3%), a measure proportional to DAT binding potential. Regression analysis of the logit transformed data enabled reliable determination of the Hill coefficient (0.51) and 50% displacement (ED₅₀) dose of cocaine (2.8 mg/kg). These preliminary data suggest that cocaine produces behavioral effects in humans at measurable levels of DAT occupancy.     

High dose cocaine use in São Paulo: a comparison of treatment and community samples

This cross-sectional study investigates patterns of drug use and associated problems among 332 cocaine users from treatment and community samples in S?o Paulo, Brazil. Data were collected using a structured questionnaire and the Severity of Dependence Scale (SDS). The majority were regular users of high doses of smoked cocaine. After controlling for severity of cocaine use, users in the community were found to be more involved in illegal activities, more likely to report adverse effects of cocaine, to be involved in prostitution, and to have lived on the streets. Better methods are required to provide interventions to tackle the problems and risk behaviors of these cocaine users.     

Individual differences in cocaine-induced locomotor activity in male Sprague–Dawley rats and their acquisition of and motivation to self-administer cocaine

Rationale  Factors that increase an individual’s susceptibility to cocaine dependence remain largely unknown. We have previously shown that adult outbred male Sprague–Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on their locomotor activity following the administration of a single dose of cocaine (10 mg/kg, i.p.). Furthermore, LCR/HCR classification predicts dopamine transporter function/inhibition, cocaine-induced locomotor sensitization, and cocaine-conditioned place preference. Objectives  The present study assessed LCR/HCR classification and the development of locomotor sensitization on the latency to acquire cocaine self-administration and motivation to self-administer cocaine. Results  LCRs and HCRs did not differ in their latency to acquire low-dose cocaine self-administration (0.25 mg/kg/infusion over 12 s, fixed ratio 1 schedule of reinforcement). In a follow-up experiment, repeated experimenter-administered injections of cocaine (10 mg/kg, i.p.) resulted in locomotor sensitization for LCRs, but not HCRs; nonetheless, all rats exhibited decreased latency to acquire cocaine self-administration compared to the first experiment. Repeated cocaine preexposure and LCR/HCR classification predicted break point when rats responded for cocaine under a progressive ratio schedule of reinforcement (0.25, 0.5, and 1.0 mg/kg/infusion; multiple exposure>single exposure, LCR>HCR), but there was no interaction between these variables. Conclusions  Although LCR/HCR classification did not predict the rate of acquisition of cocaine self-administration under these conditions, LCR rats demonstrated greater responding for cocaine after acquisition (PR). Thus, these findings demonstrate the relevance of using the LCR/HCR model when studying susceptibility to cocaine dependence.     

A comparison of medical symptoms reported by cocaine‐, opiate‐, and alcohol‐dependent patients

Substance abuse is frequently associated with adverse medical consequences. The differences in medical symptoms reported by 101 alcohol‐, 113 cocaine‐, and 107 opiate‐dependent individuals receiving outpatient treatment were studied using a 134‐item questionnaire (MILCOM). Data analysis revealed interesting and unexpected findings, with cocaine patients reporting the fewest total symptoms among the three groups. Moreover, cocaine patients reported significantly fewer CNS and musculo‐skeletal symptoms compared to both alcohol and opiate patients and significantly fewer GI and urinary symptoms than the alcohol but not the opiate patients. In addition, there were sex‐ and race‐related differences in the pattern of symptoms reported. Women reported significantly more CVS, mood, nose/throat, CNS, skin, and GI symptoms than men. Similarly, Caucasians reported significantly more mood, CNS, nose/throat, head/neck, musculoskeletal, and GI symptoms than African‐Americans. The study highlights the influence of drug of choice, gender, and race on medical needs of substance‐abusing persons.     

Parenting under the influence: The effects of opioids,alcohol and cocaine on mother–child interaction

Nearly 20% of adults receiving treatment for a substance use disorder live with their minor children (Stanger et al., 1999) and women in drug use treatment are twice as likely as men to have children in their household (Wechsberg et al., 1998). Parental drug use impacts the family through reduced family resources such as money and food, and researchers consistently note parenting deficits among substance users (Solis, Shadur, Burns, & Hussong, 2012). Little is known about differences in parenting and mother–child interaction among mothers with different drugs of choice or among mothers of older children, between 8 and 16 years. This study reports the findings from a sample of treatment seeking opioid, alcohol and cocaine using mothers and their 8–16-year-old child. Findings from a mother–child observational task and self-reported parenting measure indicated less undermining autonomy and higher mother maternal acceptance among opioid compared to alcohol addicted mothers. African American mothers were observed to have fewer negative interactional behaviors than Whites and both African American mothers and children self-reported higher firm control and maternal acceptance. Overall, mothers appeared to struggle with effective discipline with older versus younger children. Findings offer useful information to clinicians seeking to effectively tailor their interventions to women and children who present with different drugs of abuse, race/culture and developmental stage of child.