We have found that peptide antagonists of corticotropin-releasing factor (CRF) receptors attenuate reinstatement of heroin and cocaine seeking induced by footshock. Here we examined the effect of a nonpeptide, selective CRF1 receptor antagonist, CP-154,526, on reinstatement of heroin and cocaine seeking induced by footshock. Rats were trained to self-administer heroin or cocaine (0.1 and 1.0 mg/kg per infusion, i.v., respectively) for 9-12 days. Extinction sessions were given for up to 14 days, during which saline was substituted for the drugs. Tests for reinstatement were then conducted after exposure to intermittent footshock (10 or 15 min, 0.5 mA). The footshock stressor reliably reinstated extinguished cocaine- and heroin-taking behavior. Pretreatment with CP-154,526 (15 and 30 mg/kg, s.c.) significantly attenuated the reinstatement effect of the stressor in both heroin- and cocaine-trained rats. CP-154,526, administered in the absence of the footshock stressor, did not affect extinguished drug seeking. In addition, in a separate experiment, CP-154,526 was shown not to alter high rates of lever pressing for a 10% sucrose solution, suggesting that the suppression of lever pressing in stress-induced reinstatement is not caused by a performance deficit. These results extend previous reports on the role of CRF in reinstatement of drug seeking induced by stressors. The present data also suggest that, to the extent that exposure to environmental stressors provoke relapse to drug use in humans, systemically effective CRF receptor antagonists may be of use in the treatment of relapse to drug use.

These and previous data suggest that stressors may be more effective stimuli for reinstatement of behaviors previously maintained by drug reinforcers as compared with non-drug reinforcers.

The operation of a motor vehicle requires the integrity of sensory, motor, and intellectual faculties. Impairment of these faculties following the consumption of alcohol has been studied extensively through laboratory, closed-course and on-road driving, and epidemiological studies. The scientific literature was reviewed critically, with a focus on low-to-moderate blood alcohol concentrations (BAC ≤ 0.100%), to identify the most reliable determinants of alcohol-impaired driving. Variables such as age, gender, driving skill, and tolerance were shown to have limited impact on impairment. It was concluded the most relevant variables are BAC and complexity of the driving task. The scientific literature provides a high degree of confidence to support the conclusion that a BAC of 0.050% impairs faculties required in the operation of a motor vehicle. Whether impairment is apparent depends upon the complexity of the driving task, which applies to both study design and actual driving.

Objective To assess and compare the quality of pharmacoeconomic abstracts of cost-minimization analyses, cost–effectiveness analyses, cost–utility analyses, and cost-benefit analyses of original research articles in selected medical, pharmacy, and health economics journals. Methods MEDLINE was used to identify articles in selected medical, pharmacy, and health economics journals using the MeSH word “economic” and text words “cost” and “pharmacoeconomic”; the journal PharmacoEconomics was searched manually. All retrieved abstracts were evaluated. Original, comparative (at least one drug comparator) research articles (1990–1994) reporting both costs and clinical outcomes were included in the quality analysis. Abstract quality was assessed as a percentage by using a checklist with 29 objective criteria. Group consensus produced interrater reliability greater than 0.8. Results One thousand two published abstracts labeled with the above key words were identified. Of these, 951 were excluded from quality assessment because they were not original research (18%), were not pharmacoeconomic research (47%), lacked a drug comparator (35%), or did not report a clinical outcome (0.5%). Thus, the quality of 51 (5% of the total) remaining abstracts was assessed. Overall scores were 56% in 1990 and 58% in 1994 (p = 0.094). Medical articles scored highest (61.5%; n = 25), pharmacy articles were next (54.3%; n = 5), and health economics articles were lowest (53.4%; n = 21) (p = 0.091); structured abstracts scored significantly higher (62.5%; n = 20) than unstructured (53.3%; n = 31) (p = 0.003). Conclusions Abstract quality was generally poor, with no significant change in quality over time. Medical journals scored highest, probably because they use structured abstracts. Guidelines for structured pharmacoeconomic abstracts may assist in improving quality.

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