Acute marijuana effects on human risk taking.

Previous studies have established a relationship between marijuana use and risky behavior in natural settings. A limited number of laboratory investigations of marijuana effects on human risk taking have been conducted. The present study was designed to examine the acute effects of smoked marijuana on human risk taking, and to identify behavioral mechanisms that may be involved in drug-induced changes in the probability of risky behavior. Using a laboratory measure of risk taking designed to address acute drug effects, 10 adults were administered placebo cigarettes and three doses of active marijuana cigarettes (half placebo and half 1.77%; 1.77%; and 3.58% Delta9-THC) in a within-subject repeated-measures experimental design. The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky. Data analyses examined cardiovascular and subjective effects, response rates, distribution of choices between the risky and nonrisky option, and first-order transition probabilities of trial-by-trial data. The 3.58% THC dose increased selection of the risky response option, and uniquely shifted response probabilities following both winning and losing outcomes following selection of the risky option. Acute marijuana administration thereby produced measurable changes in risky decision making under laboratory conditions. Consistent with previous risk-taking studies, shifts in trial-by-trial response probabilities at the highest dose suggested a change in sensitivity to both reinforced and losing risky outcomes. Altered sensitivity to consequences may be a mechanism in drug-induced changes in risk taking. Possible neurobiological sites of action related to THC are discussed.     

Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Evasin‐3‐like anti‐chemokine activity in salivary gland extracts of ixodid ticks during blood‐feeding: a new target for tick control

Ticks exploit many evasion mechanisms to circumvent the immune control of their hosts including subversion of the communication language between cells of the immune system provided by chemokines and other cytokines. One subversive molecule secreted in the saliva of Rhipicephalus sanguineus is Evasin‐3, a structurally unique 7 kDa protein that selectively binds the neutrophil chemoattractants, CXCL8 and (with lower affinity) CXCL1. We compared anti‐human CXCL8 and anti‐mouse CXCL1/KC activities in salivary gland extracts prepared from adult Amblyomma variegatum, Rhipicephalus appendiculatus and Dermacentor reticulatus ticks during blood‐feeding. Both anti‐CXCL8 activity and anti‐CXCL1 activity were detected in all species and in both adult females and males, with consistently higher activity levels against CXCL8. These results suggest that Evasin‐3‐like activity is common amongst metastriate ixodid tick species, and provide further evidence of the importance to ticks in controlling neutrophils during blood‐feeding. As such, Evasin‐3 offers a new target for anti‐tick vaccine development.     

Acute effects of gabapentin on laboratory measures of aggressive and escape responses of adult parolees with and without a history of conduct disorder

Rationale The possible role of GABA in human aggression was evaluated by administering gabapentin to subjects with and without a history of conduct disorder and comparing the effects on laboratory measures of aggression and escape.Methods Eighteen male and two female subjects with a history of criminal behavior participated in experimental sessions, which measured aggressive and escape responses. Ten subjects had a history of childhood conduct disorder (CD+) and ten subjects with no history (non-CD controls). Aggression was measured using the Point Subtraction Aggression Paradigm (PSAP), which provided subjects aggressive, escape and monetary reinforced response options.Results Acute doses (200, 400 and 800 mg) of gabapentin had similar effects on aggressive responses among CD+ subjects compared to non-CD control subjects. Aggressive responses of CD+ and non-CD control subjects increased at lower gabapentin doses, and decreased at the highest 800 mg gabapentin dose. Gabapentin increased escape responses for both CD+ and non-CD controls CD– subjects at the lowest dose, but then produced dose-related decreases at the two higher doses in both groups. No changes in monetary reinforced responses were observed, indicative of no CNS stimulation or sedation.Conclusions Gabapentin produced similar bitonic effects upon aggressive and escape responses in subjects with and without a history of childhood conduct disorder. This is in marked contrast to prior differential effects of baclofen on aggressive responses between CD+ and non-CD control subjects in a previous study.     

Acute effects of lorazepam on laboratory measures of aggressive and escape responses of adult male parolees

Acute benzodiazepine administrations typically decrease aggressive responding, but increases in aggression have been reported in some studies. The benzodiazepine lorazepam has been studied less frequently than other benzodiazepines in aggression research, although it is often used to suppress violent aggression in patients. The present study was designed to investigate the effects of acute administrations of lorazepam on aggressive responding in adult humans on a laboratory aggression task. Eight adult males participated in experimental sessions on the Point Subtraction Aggression Paradigm (PSAP), which provided subjects with aggressive, escape and monetary-reinforced response options. Acute oral doses (1, 2 and 4 mg) of lorazepam decreased both aggressive responding and monetary-reinforced responding in seven of eight subjects. In one subject, lorazepam produced dose-dependent increases in aggressive responding. The effects of lorazepam on escape responding were the same as the effects on aggressive responding. The results are consistent with prior research using the PSAP and clinical data showing that benzodiazepines generally decrease aggression, and contrast with other studies that have shown that benzodiazepines can increase aggression. Since lorazepam affected both aggressive and escape responding, it is suggested that while lorazepam often produces sedation, it also modifies human aggressive responding, in part, by suppressing reactions to aversive stimuli.     

Acute marijuana effects on response-reinforcer relations under multiple variable-interval schedules

Acute marijuana administration may alter response-reinforcer relationships via a change in reinforcer efficacy, but may also impair coordination and motor function. One approach to evaluating drug effects on both motor function and reinforcer efficacy involves fitting the matching law equation to data obtained under multiple variable interval (VI) schedules. The present report describes an experiment that examined the effects of acute marijuana on response properties using this approach. Six human subjects responded under a multiple VI schedule for monetary reinforcers after smoking placebo and two active doses of marijuana. The low marijuana dose produced unsystematic changes in responding. As measured by the matching law equation parameters (k and rB), at the high dose five subjects showed a decrease-motor-related properties of response rate and four subjects' responding indicated a decrease in reinforcer efficacy. These data raise the possibility that, at high doses, marijuana administration alters both motor function and reinforcer efficacy.     

Individual differences in aggressive responding to intravenous flumazenil administration in adult male parolees

Nonhuman and human studies have shown that benzodiazepine (BZD) receptor agonists can modify aggressive behaviour. However, it is unknown whether flumazenil, a BZD receptor antagonist, enhances or inhibits aggressive behaviour.The present study was designed to investigate the effects of acute administrations of flumazenil on aggressive responding in adult humans.Six adult males with histories of childhood conduct disorder (DSM IV R) participated in experimental sessions. Aggression was measured using the Point Subtraction Aggression Paradigm (PSAP; Cherek 1992), which provided subjects with aggressive and monetary-reinforced response options.Acute doses of flumazenil (2 and 3mg) did not produce statistically significant changes in either monetary-reinforced responding or aggressive responding. The analysis of individual subjects data revealed that aggressive responses varied across subjects.The results are discussed in terms of individual differences based on the previous history of BZD abuse. Additional laboratory research is needed to better clarify the behavioural mechanisms by which BZD receptor antagonists modify human aggressive responding.     

Effects of acute tiagabine administration on aggressive responses of adult male parolees

Experimental and clinical studies have supported a relationship between gamma-aminobutyric acid (GABA) and aggressive behavior in non-humans and humans. Tiagabine is a GABA uptake inhibitor that has been shown to produce acute behavioral effects in animals. In addition, tiagabine has been shown to decrease aggression in agitated patients when administered chronically. The present study was designed to investigate the effects of acute administration of tiagabine on aggressive responding on a laboratory task in adult humans. Ten adult males participated in experimental sessions on the Point Subtraction Aggression Paradigm (PSAP), which provided subjects with aggressive, escape, and monetary-reinforced response options. All subjects received four acute oral doses of Tiagabine (4, 8, 12 and 16 mg) separated by placebo sessions. Tiagabine decreased aggression at doses that either did not affect, or affected to a lesser extent, monetary-reinforced responding. The results are consistent with some prior research using the PSAP showing a possible unique role for GABA in the regulation of human aggression. A possible behavioral mechanism for the rate-decreasing effects on aggressive responding produced in the present study is that tiagabine may modify aggressive responding by suppressing reactions to aversive stimuli.