Characterize The Modulatory Effects Of Dopamine D2/D3 Receptor Agonist And Antagonist Drugs On Compulsive Behaviors

Dopamine D2/D3 Receptor Agonist and Antagonist Drug Effects on Fronto-striatal Systems Related to Compulsive Behaviour in Healthy Volunteers and Patients With Addictive and Compulsive Disorders

3 groups of subjects (healthy controls, OCD subjects and stimulant-dependent subjects) will receive pramipexole (1.5 mg, single dose), amisulpride (400 mg, single dose) or placebo in a cross-over, double-blind, placebo-controlled design.

Effects of compulsive behaviour will be assessed using fMRI and cognitive testing.

Assess biomarkers including cardiovascular responses and plasma levels. All groups studied on 3 separate occasions following screening, with at least a week intervening between consecutive assessments. The procedures to be adopted for study assessment will be identical on each occasion.

Inclusion Criteria:

• Male or female, between 18 - 55 years of age; the groups will be matched for either handedness.
• Participants must have the ability to comprehend the key components of the consent form and provide informed consent.
• Participants must lead and write (in English) at a level sufficient to complete study related assessments.
• Assessment by a psychiatrist or psychologist, which includes a face-to-face evaluation of the individual using the DSM-VI diagnosis.
• No history of neurological disorder, head/brain injury, hepatitis, or visual impairment.
• No MRI contra-indications (metal in body, claustrophobia) and able to provide blood samples (venous accessibility, especially relevant for drug users).
• Patients with obsessive-compulsive disorder will have a minimum 2-year history of compulsive behaviours satisfying DSM-IV-TR criteria for OCD.
• Participants with chronic stimulant use will have a minimum 2-year history of dependence on class A stimulants, with age of drug abuse onset before 20 years, and will satisfy DSM-IV-TR criteria for dependence on stimulant drugs.
• Control volunteers have to be in good mental and physical health.

Exclusion Criteria:

• A personal history of psychiatric or neurological disorders, as defined by the DSMIV (except OCD in patients with OCD and substance dependence in drug users)

• A history or presence of alcohol / substance abuse or dependence (other than nicotine), as defined by the DSM-IV-TR (except drug dependence group).

• A BDI-II total score greater than 14 will lead to exclusion from the study.

• Treatment with methadone or buprenorphine may interfere with the experimental tasks, and therefore, will lead to exclusion from the study.

• Participants who have any laboratory abnormality that in the investigator's judgement is considered to be clinically significant and could potentially affect subject safety or study outcome.

  • History of clinically significant or current renal dysfunction.
  • Clinically significant abnormalities in hematology, blood chemistry, MRI, urinalysis or physical examination not resolved by baseline visit.
  • Impaired liver function at baseline or history of liver dysfunction.
  • Female participant is pregnant or currently breastfeeding.

• Any serious medical disorder or condition that would in the Investigator's opinion, preclude the administration of study medication and or a history of clinically significant hepatic, cardiac, renal, neurologic, cerebrovascular, metabolic or pulmonary disease.