Presynaptic subsensitivity as a possible basis for sensitization by long-term dopamine mimetics.

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Dopaminergic sensitization is a phenomenon observed with chronic dopamine agonist use.
• The underlying cellular mechanisms require further elucidation.

Purpose of the Study:

• To investigate the cellular basis of dopaminergic sensitization induced by long-term dopamine mimetics.
• To examine changes in dopamine receptor binding and function in rat striatum.

Main Methods:

• Rats received daily injections of apomorphine or amphetamine (10 mg/kg) for 14 days.
• Specific binding of 3H-apomorphine and 3H-haloperidol was measured.
• The cataleptogenic effects of haloperidol were assessed.

Main Results:

• Long-term apomorphine or amphetamine decreased 3H-apomorphine binding but did not alter 3H-haloperidol binding.
• Apomorphine treatment enhanced haloperidol's cataleptogenic action.
• Spontaneous catalepsy was observed post-apomorphine withdrawal.

Conclusions:

• Reduced 3H-apomorphine binding suggests a decrease in presynaptic dopamine receptors.
• This reduction may lead to less autoregulation and enhanced dopamine agonist effects.
• These changes potentially explain dopaminergic sensitization from long-term agonist exposure.