DRIVE TO SMOKE AND DOPAMINE BLOCKADE

Project: Research project

Project Details

Description

Nicotine's enhancement of transmission in central dopaminergic pathways
may be a primary reinforcing mechanism which drives smoking behavior. To
explore this possibility we propose to study a group of individuals, i.e.,
patients with schizophrenia, who have a prevalence of smoking more than
twice that of the general population. Certain symptoms of this disorder
are believed due to dysfunction in dopamine pathways. Drugs to treat this
disorder block dopamine receptors.

We have developed reliable and valid measures of nicotine hunger,
including cigarette self-administration sessions in which patients have
repeated determinations of expired carbon monoxide during two hours of
free access to cigarettes, and a smoke-mixing device which permits
patients to select their preferred nicotine concentrations in cigarette
smoke. We propose to measure nicotine hunger in 72 newly admitted
patients with schizophrenia during a prospective neuroleptic-free washout,
and on three subsequent occasions during a 42 day double-blind trial
comparing three pharmacologically distinct dose levels of the dopamine
receptor blocker, haloperidol. We will examine whether, and how, nicotine
hunger changes in relation to haloperidol dose and plasma level, the
unfolding of therapeutic response, and the development of extrapyramidal
side effects.

Two weeks into the double-blind haloperidol dose comparison, we will also
determine the effects of four different dose levels of nicotine
transdermal patch (O, 7, 14, or 21 mg, administered in a Latin square
design balanced for order effects) on positive and negative
psychopathology and extrapyramidal side effects.

The proposed work will substantially clarify whether the excess of smoking
in these patients reflects their efforts to treat their disease or to
counteract the unwanted effects of its pharmacotherapy. It will also
provide important information about the relationships between nicotine and
dopamine systems which could not be obtained in other populations.
StatusNot started