TY - JOUR
T1 - Nucleus accumbens serotonin1A receptors control cocaine-induced hyperactivity but not local serotonin increase: an in vivo microdialysis study
AU - Müller, C.P.
AU - Thönnessen, H
AU - De Souza Silva, M.A.
AU - Fink, H
AU - Bert, B
AU - Carey, R.J.
AU - Huston, J.P.
PY - 2004/8
Y1 - 2004/8
N2 - The nucleus accumbens (Nac) is an important structure for cocaine-induced hyperactivity and receives a dense serotonergic (5-HT) innervation. Previous studies showed that a systemic activation of 5-HT1A receptors potentiates cocaine-induced hyperlocomotion, but attenuates the cocaine-induced 5-HT increase in the Nac. In order to address the role of Nac 5-HT1A receptors in the control of cocaine-induced and spontaneous behavioural activity and local 5-HT release, we used in vivo microdialysis in freely moving rats. The 5-HT1A-receptor agonist, 8-OH-DPAT (0, 1 and 10 μM), was applied locally into the Nac by reverse dialysis followed by a cocaine (10 mg/kg) or saline i.p. injection. The Nac 5-HT1A-receptor activation potentiated cocaine-induced hyperlocomotion, but attenuated rearing behaviour dose-dependently. Parallel to that, the cocaine-induced increase in Nac 5-HT dialysate level was unaffected, as were the decreases in 5-HIAA and DOPAC dialysate levels after cocaine. In saline treated rats, the local application of 8-OH-DPAT into the Nac affected neither spontaneous behavioural activity nor 5-HT, 5-HIAA or DOPAC dialysate levels in the Nac. These data suggest that Nac 5-HT1A receptors exert a bi-directional control of cocaine-induced hyperactivity, while not affecting spontaneous behaviour. Furthermore, accumbal 5-HT1A receptors do not appear to be directly involved in the acute effects of cocaine on 5-HT, 5-HIAA or DOPAC levels in the Nac.
AB - The nucleus accumbens (Nac) is an important structure for cocaine-induced hyperactivity and receives a dense serotonergic (5-HT) innervation. Previous studies showed that a systemic activation of 5-HT1A receptors potentiates cocaine-induced hyperlocomotion, but attenuates the cocaine-induced 5-HT increase in the Nac. In order to address the role of Nac 5-HT1A receptors in the control of cocaine-induced and spontaneous behavioural activity and local 5-HT release, we used in vivo microdialysis in freely moving rats. The 5-HT1A-receptor agonist, 8-OH-DPAT (0, 1 and 10 μM), was applied locally into the Nac by reverse dialysis followed by a cocaine (10 mg/kg) or saline i.p. injection. The Nac 5-HT1A-receptor activation potentiated cocaine-induced hyperlocomotion, but attenuated rearing behaviour dose-dependently. Parallel to that, the cocaine-induced increase in Nac 5-HT dialysate level was unaffected, as were the decreases in 5-HIAA and DOPAC dialysate levels after cocaine. In saline treated rats, the local application of 8-OH-DPAT into the Nac affected neither spontaneous behavioural activity nor 5-HT, 5-HIAA or DOPAC dialysate levels in the Nac. These data suggest that Nac 5-HT1A receptors exert a bi-directional control of cocaine-induced hyperactivity, while not affecting spontaneous behaviour. Furthermore, accumbal 5-HT1A receptors do not appear to be directly involved in the acute effects of cocaine on 5-HT, 5-HIAA or DOPAC levels in the Nac.
U2 - 10.1016/j.neuropharm.2004.03.020
DO - 10.1016/j.neuropharm.2004.03.020
M3 - Article
VL - 47
SP - 205
EP - 215
JO - Neuropharmacology
JF - Neuropharmacology
IS - 2
ER -