Project: Research project

Project Details


DESCRIPTION: (Applicant's Abstract)

Studies of the etiology of addiction have been limited in part by difficulty
in obtaining homogeneous addiction populations, reinforcing the need to
develop new pathophysiological models of addiction. Pathological gambling
(PG) is a chronic, disabling, and understudied impulse control disorder
which affects 1-3% of the population. PG is often viewed as an addiction,
consisting of tolerance, dependence, and withdrawal. Up to half of
pathological gamblers have substance use problems.

Prior studies have suggested serotonergic and noradrenergic abnormalities in
PG. Our pharmacological treatment studies with the serotonin reuptake
blocker fluvoxamine revealed a reduction in actual pathological gambling
behavior. In pilot pharmacological challenge studies, the partial 5-HT
agonist m-CPP induced a "high" behavioral response and an augmented
prolactin response in PG patients compared to normal controls. The alpha-2
agonist clonidine induced an augmented growth hormone response in PG. This
pattern of response, not seen before in other impulsive, compulsive, and
depressive conditions, may reflect behavioral initiation/ disinhibition and
behavioral readiness, respectively, key features of PG relevant to

To examine serotonergic and noradrenergic responsiveness in PG, this
proposal will compare 70 PG patients (35 males, 35 females) and 40 normal
controls (20 males, 20 females) of comparable marginal distribution of age,
sex, SES, and ethnicity on behavioral (high) and neuroendocrine (prolactin,
GH) response to m-CPP and clonidine, controlling for pulsatile
neuroendocrine factors. Specificity of noradrenergic and serotonergic
systems with regard to behavioral readiness vs. behavioral
initiation/disinhibition, respectively, will be examined. Severity of
impulsivity and depression will be correlated with these serotonergic and
noradrenergic measures. Understanding the etiology of PG will facilitate
the development of pathophysiological models of addiction.
Effective start/end date5/10/974/30/02


  • Pharmacology
  • Psychiatry and Mental health