Dopaminergic challenges in social anxiety disorder: evidence for dopamine D3 desensitisation following successful treatment with serotonergic antidepressants.
Serotonergic antidepressants (SSRIs) are first-line treatments for social anxiety disorder [SAnD], though there is evidence of dopaminergic system dysfunction. Twenty subjects with DSM-IV SAnD, untreated (n = 10) and SSRI-remitted DSM-IV SAnD (n = 10), were administered a single dose of 1) a dopamine agonist (pramipexole 0.5 mg) and 2) a dopamine antagonist (sulpiride 400 mg), followed by anxiogenic challenges (verbal tasks and autobiographical scripts) in a double-blind crossover design, the two test days being one week apart. Anxiety symptoms were measured by self-reported changes in Visual Analogue Scales, specific SAnD scales and anxiety questionnaires. Plasma levels of prolactin were obtained. Untreated SAnD subjects experienced significant increases in anxiety symptoms following behavioural challenges after either sulpiride or pramipexole. Following remission with SSRIs, the socially anxiogenic effect of behavioural provocation was significantly attenuated under pramipexole, whereas under sulpiride effects remained significantly elevated. There appears to be instability of the dopamine system under behavioural stress in social anxiety subjects that is only partly rectified by successful treatment with an SSRI, which may induce a desensitisation of postsynaptic dopamine D(3) receptors.
Hood
S D
SD
School of Psychiatry and Clinical Neurosciences (M521), University of Western Australia, Perth, Australia. sean.hood@uwa.edu.au
Potokar
J P
JP
Davies
S J C
SJ
Hince
D A
DA
Morris
K
K
Seddon
K M
KM
Nutt
D J
DJ
Argyropoulos
S V
SV
D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D052160:Benzothiazoles / Q000009:adverse effects / Q000627:therapeutic use; D018592:Cross-Over Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077487:Pramipexole; D011388:Prolactin / Q000097:blood; D020033:Protein Isoforms / Q000819:agonists / Q000037:antagonists & inhibitors; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D013315:Stress, Psychological; D013469:Sulpiride / Q000009:adverse effects / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult
D052160:Benzothiazoles; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D000077487:Pramipexole; D011388:Prolactin; D020033:Protein Isoforms; D050637:Receptors, Dopamine D3; D017367:Selective Serotonin Reuptake Inhibitors; D013469:Sulpiride; C493593:DRD3 protein, human