Serotonin1A-receptor agonism attenuates the cocaine-induced increase in serotonin levels in the hippocampus and nucleus accumbens but potentiates hyperlocomotion: an in vivo microdialysis study.

The hippocampus and the nucleus accumbens (Nac) are important structures for the modulation of spontaneous locomotor activity. Both structures receive a serotonergic (5-HT) innervation. We have previously reported that the 5-HT(1A)-receptor antagonist WAY 100635 blocked cocaine-induced hyperactivity, while potentiating cocaine-induced 5-HT increases in the hippocampus and the Nac. In order to further investigate the relationship between extracellular 5-HT concentration and cocaine-induced behaviour, we used in vivo microdialysis to measure the effects of the 5-HT(1A)-receptor agonist 8-OH-DPAT on cocaine-induced changes in the extracellular 5-HT concentration in the hippocampus and the Nac and on behavioural activity. Following a pilot pretest in which we determined the lowest effective dose of 8-OH-DPAT for potentiating cocaine-induced hyperlocomotion, four groups of rats were given one of the following drug treatments: 8-OH-DPAT (0.2 mg/kg) and cocaine (10 mg/kg), saline and cocaine (10 mg/kg), 8-OH-DPAT (0.2 mg/kg) and saline, or saline and saline. The injections were administered i.p. and spaced 30 min apart. We found that the 5-HT(1A)-receptor agonist 8-OH-DPAT attenuated the cocaine-induced increases in 5-HT in the hippocampus and the Nac, but potentiated cocaine-induced hyperlocomotion. 5-HT metabolite measurements revealed a complex role for the 5-HT(1A)-receptor in the broad spectrum of cocaine's neurochemical effects. Altogether, these observations support an important role of the 5-HT(1A)-receptor in the hippocampus and Nac in the modulation of cocaine stimulant effects.