The partial D2-like dopamine receptor agonist terguride acts as a functional antagonist in states of high and low dopaminergic tone:: evidence from preweanling rats

Rationale: In adult rats, the partial D-2-like agonist terguride acts as an antagonist at normosensitive D-2-like post-synaptic receptors, while it acts as an agonist at the same receptors during states of low dopaminergic tone. Objective: The purpose of the present study was to determine whether partial D2-like agonists exhibit both antagonistic and agonistic actions during the preweanling period. Methods: In experiments 1 and 2 (examining the agonistic actions of terguride), preweanling rats were either given an escalating regimen of amphetamine to induce a state of amphetamine withdrawal or pretreated with the tyrosine hydroxylase inhibitor AMPT. Distance traveled was measured after rats were injected with saline, terguride (0.4-1.6 mg/kg), or the full D-2-like receptor agonist NPA (0.01 mg/ka). In experiment 3 (examining the antagonistic actions of terguride), preweanling rats were pretreated with terguride 30 min before they were tested with saline, NPA (0.05 mg/kg), or amphetamine (1.5 mg/kg). Results: NPA had an exaggerated locomotor activating effect when tested under conditions of amphetamine withdrawal, while the partial D-2-like agonist did not enhance distance traveled under any circumstance. Similarly, NPA increased and terguride did not affect the distance-traveled scores of AMPT-pretreated rats. In experiment 3, terguride pretreatment significantly reduced the distance traveled of amphetamine-treated and NPA-treated rats. Conclusions: The behavioral evidence indicates that, during the preweanling period.. terguride antagonizes D-2-like post-synaptic receptors in a state of high dopaminergic tone; however, there is no evidence that terguride is capable of stimulating D-2-like post-synaptic receptors during states of low dopaminergic tone.