Mesolimbic 7-OH-DPAT affects locomotor activities in rats

This study tested the hypotheses that the dopamine D3 receptor is both an autoreceptor and a postsynaptic receptor and has an affinity for dopamine at the nanomolar level. The effect of bilateral microinjections of a dopamine D3-like agonist, 7-OH-DPAT, into the nucleus accumbens and into the ventral tegmental area (VTA) was tested with rats in activity monitors. Horizontal movement, rearing, and stereotypy times in seconds were automatically measured during 12 consecutive 10-min time blocks. Intraaccumbens 7-OH-DPAT (0.0001-10.0 micrograms/side) resulted in a highly significant dose by time block interactions. The dose of 0.0001 microgram/side resulted in the potentiation of horizontal movement time during the time blocks 10-40 min; whereas, 0.001-1.0 microgram/side potentiated locomotion during the early blocks following the 10-min interval. However, 10.0 micrograms/side resulted in a biphasic effect, attenuation followed by potentiation. 7-OH-DPAT (0.0001-1.0 microgram/ side) potentiated rearing time in the early time blocks and (0.001-10.0 micrograms/side) attenuated stereotypy time during the first 20 min time blocks. On the other hand, intra-VTA 7-OH-DPAT (10.0 micrograms/side) attenuated horizontal movement time during the first 20-min time blocks and (0.01 and 0.0001 microgram/side) potentiated movement time at the 20-min time block. Intraventral tegmental area 7-OH-DPAT had no effects on rearing and stereotypy times. These data support the hypothesis that the D3 receptor has an affinity for dopamine at the nanomolar level and question the hypothesis that the D3 receptors are both autoreceptors and postsynaptic receptors.