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National Institute on Drug Abuse

Director's Report to the National Advisory Council on Drug Abuse
September, 1996

Research Findings

Behavioral Research

Airway Sensory Factors Alone Produce Positive Mood Effects In Cigarette Smokers

In a recent experiment, investigators at Duke University compared the mood effects produced by a standard 1-mg nicotine cigarette versus a denicotinized cigarette. As other studies have shown, subjects reported feeling more calm and less irritable after smoking the cigarette containing nicotine. However, subjects reported many positive subjective effects after smoking the denicotinized cigarette, effects which were in fact comparable in magnitude to the nicotine cigarette. The authors conclude that the airway sensory effects of cigarette smoke alone contribute to the positive subjective effects of smoking. These results further suggest that airway sensory replacement therapy may be useful for smoking cessation. Westin, E.C., Frederique, M.B., and Rose, J.E. Pharmacology Biochemistry and Behavior. 53, pp. 309-315, 1996.

Mechanisms Mediating the Actions of Caffeine

Dr. Stephen Holtzman's research is using behavioral measures to characterize the receptor subtypes and neuronal substrates mediating caffeine's actions. A number of studies from his laboratory have used locomotor activity and the 6-hydroxydopamine unilateral nigral lesion model of rotational behavior to study caffeine's actions. A recent paper "Comparison of the Effects of Prototypical Behavioral Stimulants on Locomotor Activity and Rotational Behavior in Rats", Pharmacology, Biochemistry, and Behavior, 54, pp. 469-477, 1996, demonstrated differences in potency and efficacy of four stimulants, apomorphine, caffeine, d-amphetamine, and cocaine and a D1 agonist SKF-38393 on these two behaviors. Caffeine-induced rotation occurred over a narrow range of doses whereas the dose range for caffeine induced stimulation of locomotor activity was much broader. By contrast, SKF-38393 was more potent and effective in increasing rotational behavior than it was in increasing locomotor activity. The differences in drug effects on rotational behavior compared to locomotor activity suggest that these two behaviors involve different neuronal substrates.

Stress Modulates the Effects of Opiates

Researchers at the University of Chicago are studying how stress or pain modulate the analgesic and reinforcing effects of the opioid analgesic fentanyl, in normal volunteers. Dr. James Zacny's data show that the effect of opioids on mood and pain relief are modified by environmental context. The degree of stress and pain in the context in which opiates are self-administered determine the actual euphoric and analgesic effects of the drugs. During stress, fentanyl is chosen at above chance levels, and for its analgesic properties. With no stress present, fentanyl is not chosen more often than chance.

Behavioral Effects of Inhalants

Ongoing work being conducted at the Medical College of Virginia by Dr. Robert Balster is examining the behavioral teratology of abused inhalants in mice with use of various behavioral testing procedures. The project is specifically examining the neurobehavioral effects of the alkylbenzenes (e.g., benzene and toluene). Dr. Balster has found that many of the abused solvents and volatile anesthetics have a profile of behavioral and pharmacological effects similar to depressant drugs (barbiturates) and alcohol. In particular, the well-known anti-anxiety effect of depressants was also found in the solvents (e.g., lengthened time to enter arms of a plus maze).

Dr. Balster also has found that the volatile anesthetics produce ethanol-like discriminative effects in mice. These findings have led to his recommendations that volatile anesthetics be classified along with abused solvents as having depressant-like abuse potential. Finally, Dr. Balster has demonstrated fetal effects of trichloroethane when administered in utero to mice. This is evidence, with use of an animal model, of "fetal solvent syndrome". European Journal of Pharmacology, In Press; Pharmacology, Biochemistry and Behavior, In Press.

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