SPONTANEOUS AND DRUG-STIMULATED LOCOMOTOR-ACTIVITY AFTER THE ADMINISTRATION OF PERTUSSIS TOXIN INTO THE VENTRAL TEGMENTAL AREA

Pertussis toxin (PTX) injected into the ventral tegmental area (VTA) p roduces an enhanced locomotor response to amphetamine, In the present study, we have evaluated the role of dopamine receptors on spontaneous locomotor activity and the enhanced locomotor response to dopaminergi c agonists after the administration of PTX into the VTA. PTX injected into the VTA of rats produced a delayed increase in spontaneous locomo tor activity with a latency of 4 d. This activity was markedly increas ed by day 6 and remained elevated for at least 28 d after PTX treatmen t, This increased spontaneous locomotor activity of PTX-treated animal s was antagonized by the administration of the D-1 receptor antagonist SCH23390 (0.03 and 0.1 mg/kg sc), but not by the D-2 receptor antagon ist eticlopride (0.1 and 0.3 mg/kg sc). After adaptation to the locomo tor cages, the animals showed a markedly enhanced motor response to am phetamine (0.5 mg/kg ip) and apomorphine (5 mg/kg sc), The heightened locomotor responses to these dopaminergic agonists could be elicited f or at least 2 mo after PTX administration. The enhanced response to am phetamine was antagonized by the administration of SCH23390 (0.03 and 0.1 mg/kg sc), bat not by eticlopride (0.1 mg/kg), The increased respo nse to apomorphine in PTX-treated animals was inhibited by SCH23390 (0 .1 mg/kg sc) and partially inhibited by eticlopride (0.1 mg/kg sc), Bo th of these antagonists inhibited the spontaneous and the drug-induced locomotor responses in vehicle-treated control animals. These results suggest that the administration of PTX into the VTA leads to an incre ase in spontaneous and drug-induced locomotor activity in which D-1 re ceptors seem to play an important role.