Role of dopaminergic system(s) in mediation of the behavioural effects of bombesin

To test the effects of dopamine receptor blockade on bombesin (BN)-induced behavioural changes, adult male Sprague-Dawley rats were administered fluphenazine (0.01, 0.025, 0.1, 0.25 mg/kg, IP) followed 30 min later by BN (1 μg in 5 μl) or saline (5 μl) intracerebroventricularly (ICV). Subsequent behavioural effects were monitored in chambers equipped with strategically located infrared beam grids, controlled by a microprocessor. The following behaviours were monitored: locomotor activity (distance traversed), floor activity (horizontal or lateral displacement) and rearing activity (frequency of vertical displacement extending 17.8 cm above the floor). At all but the highest dose (0.25 mg/kg, which suppressed floor activity), fluphenazine failed to significantly alter any of the behavioural parameters monitored. Whereas at doses of 0.025 or lower, fluphenazine failed to alter BN-induced behavioural output, at doses of 0.1 mg/kg or greater, it significantly blocked the behavioural effects BN. In the next experiment, dopamine neurons of adult male Sprague-Dawley rats were lesioned using 6-hydroxydopamine (6-OHDA) (250 μg/10 μl, ICV). The 6-OHDA and sham-lesioned (control) rats were administered BN (0.001, 0.01, 0.1 or 1.0 μg, ICV) and their behaviour monitored. In the control animals, BN stimulated locomotor, floor and rearing activity in a dose-dependent manner. However, these behavioural effects of BN were markedly attenuated or absent in the 6-OHDA-lesioned animals. These data further support our contention that centrally administered BN may mediate its behavioural effects, through the dopaminergic system(s).