Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Antipsychotic Drugs in Healthy Humans

Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Antipsychotic Drugs in Healthy Humans

We hypothesized that short-term treatment with AP drugs induces insulin resistance through a mechanistic route that is independent of weight gain and that atypical drugs exert stronger effects than typical compounds in this respect. We therefore treated healthy non-obese men with olanzapine (atypical AP) or haloperidol (typical AP) for 8 days, and studied the impact of these interventions on glucose and lipid metabolism by hyperinsulinemic euglycemic clamp, isotope dilution technology and indirect calorimetry.

Inclusion Criteria:

• Healthy men, with and without a positive family history of schizophrenia.
• 20 kg/m2 < BMI < 26 kg/m2
• Age 20-40 years
• Fasting plasma glucose < 6 mmo/L

Exclusion Criteria:

• FPG > 6 mmol/L
• BMI > 26 kg/m2
• Psychiatric disorders and/or use of antipsychotic or antidepressants drugs at present or in the past.
• Any significant chronic disease
• Renal, hepatic or endocrine disease
• Use of medication known to influence lipolysis and/or glucose metabolism
• Total cholesterol > 7mmol/L and/or triglycerides > 2 mmol/L
• Recent weight changes or attempts to loose weight (> 3 kg weight gain or loss, within the last 3 months)
• Difficulties to insert an intravenous catheter
• Smoking (current)
• Severe claustrophobia (ventilated hood)
• Recent blood donation (within the last 2 months)
• Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year
• Extensive sporting activities (more than 10 hours of exercise per week)