Desflurane, enflurane, isoflurane and ether produce ethanol-like discriminative stimulus effects in mice.

In the present studies, drug discrimination procedures were used to compare the discriminative stimulus effects of ethanol (ETOH) and several volatile anesthetics. Male albino mice were trained to discriminate between IP injections of ETOH (1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 (FR20) schedule of food presentation. Stimulus generalization was examined after 20-min inhalation exposures to desflurane (4,000-32,000 ppm), enflurane (3,000-12,000 ppm), isoflurane (1,000-8,000 ppm) and ether (4,000-32,000 ppm). Concentration-related increases in ETOH-lever responding were observed for all four volatile anesthetics. For enflurane and ether, maximal levels of > 85% ETOH-lever responding were obtained at one or more concentrations. For desflurane and isoflurane, the maximal mean percentages of ETOH-lever responding were somewhat lower, but 6 out of 7 mice showed full substitution with desflurane and 5 out of 7 for isoflurane. The shared discriminative properties of these compounds with ETOH suggest that these anesthetics may share some of ETOH's pharmacological properties. These results are similar to previous research results showing ETOH-like discriminative stimulus effects in mice with other anesthetics and abused volatile inhalants (i.e. halothane, toluene and 1.1,1-trichloroethane) and may reflect the CNS-depressant drug-like effects of inhaled anesthetics and abused solvents.

Drug abuse potential evaluation in animals.

Animal laboratory studies can provide useful information concerning the potential of drugs for abuse. Over the past 50 years, methods have been developed for use with animal subjects which allow the evaluation of pharmacological properties of drugs which are particularly relevant to their abuse. The methods for preclinical drug abuse liability testing are reviewed under six heading: (1) establishment of the degree of pharmacological equivalence to known drugs of abuse, (2) drug discrimination studies, (3) tests of tolerance and cross-tolerance, (4) tests of physical dependence capacity, (5) drug self-administration tests of reinforcing effects, and (6) evaluation of toxicity and performance impairment at self-administered doses. Preclinical studies can be helpful early in drug development to select lead compounds with low abuse potential for further study. In the case of new or already marketed medications, animal testing can often compliment and extend abuse liability evaluation in human subjects. The results of abuse potential evaluation studies can be useful in making decisions about the possible need for regulation under national and international drug laws, and thus play an important role in drug abuse prevention.

Abuse potential of buspirone and related drugs.

Scientific evidence regarding the drug abuse potential of buspirone and gepirone is reviewed. In animal studies, the pharmacologic profile of buspirone differs from that of other classes of abused drugs. Buspirone does not share discriminative stimulus effects with abused depressants, and it is not self-administered. New data are presented showing a lack of reinforcing effects for gepirone in rhesus monkeys when the drug was evaluated in an intravenous drug self-administration procedure. Studies of the acute effects of buspirone conducted in human subjects provide no evidence of abuse potential, and there is no indication that the drug has been abused to any extent since being marketed in December 1986. Available evidence suggests that the azapirones buspirone and gepirone have little, if any, potential for abuse.

Abuse potential evaluation of inhalants.

Although inhalant abuse remains an important worldwide drug abuse problem, little is known about the relative abuse liability of specific inhalant compounds. This paper reviews approaches which might be used to investigate the abuse potential of inhalants in the laboratory, focusing primarily on animal studies. The principal approaches considered are inhalant self-administration and discrimination studies. A need is identified for further investigations of the abuse potential of inhalants to provide data which should be useful in shaping a more effective public health response to inhalant abuse.

Opioids: similarity between evaluations of subjective effects and animal self-administration results.

Abuse potential studies of 33 morphine-like analgesics were compared in humans and monkeys. The results of intravenous self-administration studies in rhesus monkeys were correlated with measures of morphine-like signs, symptoms, and subjective effects in ex-addicts. Each set of data was assigned to a position in a 3 x 3 contingency table dependent upon whether the results were yes, no, or equivocal. Of the 33 drugs, 29 were given identical classifications in both the human and animal test procedures. This good concordance between the human and animal results further validates each procedure and suggests the possibility that both the human and animal procedures are measuring a common underlying pharmacological property which relates to abuse potential of drugs.