The partial dopamine D2-like receptor agonist terguride functions as an agonist in preweanling rats after a 5-day reserpine regimen.

RATIONALE

Treating children and adolescents with partial D2-like agonists is becoming increasingly common, although few developmental animal studies have assessed the psychopharmacology of this class of drug. Contrary to results from adult rat studies, it has been reported that partial D2-like agonists may not induce agonist-like behavioral effects in preweanling rats during states of low dopaminergic tone.

OBJECTIVE

The purpose of the present study was to determine whether a partial D2-like agonist would act as an agonist in preweanling rats after a 5-day regimen of the dopamine-depleting agent reserpine or the tyrosine hydroxylase inhibitor alpha-methyl-DL-p-tyrosine (AMPT).

METHODS

Sprague-Dawley rats were pretreated with reserpine (1 mg kg(-1) per day) or AMPT (3 x 200 mg kg(-1) per day) on postnatal day (PD) 16-PD 20. Either 2 h (AMPT) or 5 h (reserpine) after the last pretreatment injection, rats were treated with saline, the partial D2-like agonist terguride, or the full D2-like agonist R(-)-propylnorapomorphine (NPA). Distance traveled and repetitive motor movements were measured for 60 min.

RESULTS

After repeated reserpine treatment, both terguride and NPA increased the distance-traveled scores of preweanling rats; however, only NPA, but not terguride, increased distance-traveled scores after a 5-day regimen of AMPT or an acute injection of reserpine.

CONCLUSIONS

It is now apparent that partial D2-like agonists are capable of inducing agonist-like behavioral effects in preweanling rats during a state of low dopaminergic tone. For agonistic actions to be observed, the pretreatment regimen must result in substantial and prolonged dopamine depletion.