Details

Autor(en) / Beteiligte

• Homberg, Judith R.
• De Boer, Sietse F.
• Raasø, Halfdan S.
• Olivier, Jocelien D. A.
• Verheul, Mark
• Ronken, Eric
• Cools, Alexander R.
• Ellenbroek, Bart A.
• Schoffelmeer, Anton N. M.
• Vanderschuren, Louk J. M. J.
• De Vries, Taco J.
• Cuppen, Edwin

Titel

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

Ist Teil von

• Psychopharmacologia, 2008-10, Vol.200 (3), p.367-380

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2008

Link zum Volltext

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• Rationale While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood. Objectives To study the rewarding and motivational properties of cocaine in the serotonin transporter knockout (SERT −/− ) rat and the involvement of compensatory changes in 5-HT 1A receptor function are the objectives of the study. Materials and methods The SERT −/− rat was tested for cocaine-induced locomotor activity, cocaine-induced conditioned place preference, and intravenous cocaine self-administration. In addition, the function and expression of 5-HT 1A receptors was assessed using telemetry and autoradiography, respectively, and the effect of 5-HT 1A receptor ligands on cocaine’s psychomotor effects were studied. Results Cocaine-induced hyperactivity and conditioned place preference, as well as intravenous cocaine self-administration were enhanced in SERT −/− rats. Furthermore, SERT −/− rats displayed a reduced hypothermic response to the 5-HT 1A receptor agonist 8-OHDPAT. S-15535, a selective somatodendritic 5-HT 1A receptor agonist, reduced stress-induced hyperthermia (SIH) in wild-type controls (SERT +/+ ), while it increased SIH in SERT −/− rats. As 5-HT 1A receptor binding was reduced in selective brain regions, these thermal responses may be indicative for desensitized 5-HT 1A receptors. We further found that both 8-OHDPAT and S-15535 pretreatment increased low-dose cocaine-induced locomotor activity in SERT −/− rats, but not SERT +/+ rats. At a high cocaine dose, only SERT +/+ animals responded to 8-OHDPAT and S-15535. Conclusion These data indicate that SERT −/− -associated 5-HT 1A receptor adaptations facilitate low-dose cocaine effects and attenuate high-dose cocaine effects in cocaine supersensitive animals. The role of postsynaptic and somatodendritic 5-HT 1A receptors is discussed.