Noradrenergic function in pathological gambling: blunted growth hormone response to clonidine.
The noradrenergic system has been linked to impulsive behaviour in animals and humans, yet little data on noradrenergic system exist in specific impulse control disorders. To explore the role of the noradrenergic system in pathological gamblers (PG), we assessed neuroendocrine growth hormone (GH) response to the alpha2-adrenergic receptor agonist clonidine and placebo in PG and controls. The net effects of clonidine are a decrease in neurotransmission by depressing locus coeruleus activity and stimulation of GH secretion through activation of post-synaptic alpha2-adrenergic receptors in the hypothalamus. Twenty-nine PG subjects, free of other comorbid conditions, and 27 healthy controls received a double-blinded, placebo-controlled, single dose of oral clonidine (0.15 mg/kg). Data observed included GH, clonidine levels and levels of the main noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (MHPG). The area under the curve for GH response to clonidine was significantly lower (separate variance t with 44.3 df = 2.626, P = 0.012, d = 0.58) in the PG group (199.6) than in the control group (426.3). PG had significantly blunted GH responses compared with controls at 120 and 150 min post-clonidine. These results are consistent with the idea that the subsensitivity of post-synaptic alpha-2 receptors is possibly attributable to higher-than-normal noradrenergic secretion in PG. This peripheral noradrenergic dysfunction could be consistent with attenuated cortico-frontal noradrenergic function as shown in positron emission tomography (PET) studies of PG.
Pallanti
S
S
Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, USA. stefano.pallanti@mssm.edu
Bernardi
S
S
Allen
A
A
Chaplin
W
W
Watner
D
D
DeCaria
C M
CM
Hollander
E
E
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D003000:Clonidine / Q000494:pharmacology*; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000378:metabolism* / Q000503:physiopathology; D004311:Double-Blind Method; D005715:Gambling; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D009490:Neurosecretory Systems / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
D018341:Receptors, Adrenergic, alpha-2; D019382:Human Growth Hormone; D003000:Clonidine