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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