Phencyclidine: behavioral and biochemical evidence supporting a role for dopamine

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Phencyclidine (PCP) exhibits behaviors suggesting it's an indirectly acting dopamine (DA) agonist with anticholinergic properties.
• PCP inhibits monoamine uptake and stimulates striatal tyrosine hydroxylase activity through dopamine release.

Purpose of the Study:

• To elucidate the mechanism of dopamine release induced by PCP.
• To compare PCP's mechanism of action with other stimulants like methylphenidate and amphetamine.
• To investigate the role of nigrostriatal impulse flow in PCP's effects.

Main Methods:

• In vitro studies assessing monoamine uptake inhibition.
• In vitro studies measuring synaptosomal striatal tyrosine hydroxylase activity.
• In vivo studies examining haloperidol-induced dopamine metabolism potentiation.
• Behavioral studies observing PCP-induced stereotypy and turning.

Main Results:

• PCP is a potent, competitive inhibitor of monoamine uptake.
• PCP stimulates DA release, affecting tyrosine hydroxylase activity.
• PCP potentiates haloperidol-induced DA metabolism, an effect blocked by baclofen, indicating nigrostriatal pathway involvement.
• PCP releases a DA pool that inhibits DA synthesis via a feedback mechanism.

Conclusions:

• PCP acts as an indirect dopamine agonist with a unique mechanism of dopamine release.
• PCP shares similarities with nonamphetamine stimulants but possesses distinct characteristics.
• Behavioral and biochemical data caution against strict classification of PCP within the nonamphetamine stimulant class.