Hippocampus 5-HT(1A)-receptors attenuate cocaine-induced hyperlocomotion and the increase in hippocampal but not nucleus accumbens 5-HT.
Cocaine induces an increase in hippocampal and nucleus accumbens (Nac) serotonin (5-HT) concentration parallel to locomotor activation. Both effects can be modulated by systemic 5-HT(1A)-receptor agonism/antagonism. Given the contribution of the hippocampus to spontaneous behavioral activity, these observations suggest a role for hippocampal 5-HT as well in the modulation of cocaine effects on behavior. To determine the role of hippocampal 5-HT(1A)-receptors in cocaine effects on behavior and hippocampal 5-HT release, we used in vivo microdialysis in freely moving rats. The 5-HT(1A)-receptor agonist, 8-OH-DPAT (0, 0.1, 1 and 10 microM), was applied locally into the hippocampus by reversed dialysis followed by a cocaine (10 mg/kg) or saline i.p. injection. The hippocampal 5-HT(1A)-receptor activation attenuated cocaine-induced hyperlocomotion and rearing behavior dose-dependently. Parallel to that, the cocaine-induced 5-HT increase was attenuated dose-dependently in the hippocampus but was left unaffected in the Nac. The intra-hippocampal application of 8-OH-DPAT affected neither behavioral activity nor 5-HT concentration in the hippocampus and in the Nac. In accord with these findings, hippocampal 5-HT(1A)-receptors may not be directly involved in the regulation of spontaneous behavior or basal 5-HT concentration in the hippocampus and Nac. However, the results indicate an inhibitory role of hippocampal 5-HT(1A)-receptors in cocaine-induced hyperactivity and in the 5-HT increase evoked by cocaine in the hippocampus but not in the Nac.
Institute of Physiological Psychology I and Center for Biological and Medical Research, University of Düsseldorf, Düsseldorf, Germany.
Christian P
CP
Müller
Heike
H
Thönnessen
Marilia
M
Barros
Carlos
C
Tomaz
Robert J
RJ
Carey
Joseph P
JP
Huston
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003042:Cocaine