Modulation of dopamine receptor sensitivity by estrogen

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• Postmenopausal females exhibit the highest incidence of tardive dyskinesia.
• Loss of ovarian function may increase susceptibility to tardive dyskinesia.
• Estrogens have been reported to reduce abnormal movements associated with tardive dyskinesia.

Purpose of the Study:

• To investigate the effects of estrogen on tardive dyskinesia using an animal model.
• To determine if estrogen can attenuate the development or manifestation of drug-induced supersensitive dopamine receptors.

Main Methods:

• Ovariectomized rats were administered haloperidol (Haldol) or Haldol + estradiol benzoate (EB) daily for 16 days.
• Following a 1-week cessation period, rats were challenged with d-amphetamine or apomorphine.
• Drug-induced stereotypy was measured to assess behavioral responses.

Main Results:

• Chronic haloperidol or EB treatment alone enhanced responses to d-amphetamine and apomorphine.
• Combined Haldol + EB treatment produced a synergistic response.
• Daily EB treatment following chronic Haldol administration attenuated drug-induced stereotypy.

Conclusions:

• Estrogen demonstrates potential to attenuate the development of tardive dyskinesia.
• Estrogen may mask the display of supersensitive dopamine receptors.
• These findings suggest a neuroprotective role for estrogen in movement disorders.