PMID- 21763429 OWN - NLM STAT- MEDLINE DCOM- 20111229 LR - 20110902 IS - 1095-9572 (Electronic) IS - 1053-8119 (Linking) VI - 58 IP - 3 DP - 2011 Oct 1 TI - Differential response to specific 5-Ht(7) versus whole-serotonergic drugs in rat forebrains: a phMRI study. PG - 885-94 LID - 10.1016/j.neuroimage.2011.06.089 [doi] AB - We recently suggested that serotonin 7 (5-Ht7) receptors may play a role in ADHD-like symptoms, at least in animal models. A mixed 5-Ht(1a/7) agonist, 8-OH-DPAT, counteracted the augmented levels of basal impulsivity, observed after treatment with a selective 5-Ht7 antagonist, SB269970 (Leo et al., 2009). In the present study, these serotonergic compounds were investigated by pharmacological magnetic resonance imaging (phMRI) at 4.7 T in adult isoflurane-anaesthetized rats. Axial echo-planar images were collected from the prefrontal cortex (PFC), ventral (nucleus accumbens, NAcc) and dorsal (dStr) striata, the hippocampus and the thalamus. After consecutive image collection for 30 min (50 baseline images), adult rats received either SB269970 (3mg/kg), 8-OH-DPAT (0.06 mg/kg) or saline intra-peritoneally (i.p.) via a remote cannula; the images were then collected for further 30 min (50 post-treatment images). Data were analysed 1) through an activation map generated on brain templates, obtained by using animals from each experimental group; 2) by a two-way ANOVA for the evaluation of temporal profiles, extracted within selected ROIs of each animal. Both compounds increased the BOLD signal in the areas of interest: SB269970, the selective 5-Ht7 antagonist, induced a significant effect in the PFC, particularly the orbital (oPFC) region, and in the NAcc. This effect started 6 to 12 min after drug administration, reached a maximum (+2.8%/+2.3%) at 12 to 18 min, and then moved to the dorsal thalamic nuclei. In contrast, the effects of 8-OH-DPAT were first observed in midline thalamic nuclei, and later appeared in forebrain regions: its effects were modest and transient within the NAcc and oPFC (+1.7% at 18 to 24 min after injection), whereas they were higher and long-lasting in the dStr and PFC, specifically the medial (mPFC) region (+3.1%/+4.0% from 15 min after drug administration onwards). The brain BOLD changes, reported as a consequence of selective 5-Ht7 antagonist administration, seemed restricted to the oPFC, NAcc and dorso-thalamic circuits, whereas the non-selective blockade of serotonergic receptors affected the mPFC, dStr and mid(line)-thalamic circuitry. The present findings revealed two differential serotonergic sub-pathways, as evidenced by the detection of physiological vascular feedback and/or neuronal activation. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Canese, Rossella AU - Canese R AD - Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy. FAU - Marco, Eva M AU - Marco EM FAU - De Pasquale, Francesco AU - De Pasquale F FAU - Podo, Franca AU - Podo F FAU - Laviola, Giovanni AU - Laviola G FAU - Adriani, Walter AU - Adriani W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110708 PL - United States TA - Neuroimage JT - NeuroImage JID - 9215515 RN - 0 (Receptors, Serotonin) RN - 0 (Serotonin Agents) RN - 0 (serotonin 7 receptor) RN - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin) SB - IM MH - 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology MH - Animals MH - Brain Mapping/*methods MH - Image Processing, Computer-Assisted MH - Magnetic Resonance Imaging MH - Male MH - Neural Pathways/drug effects/metabolism MH - Prosencephalon/*drug effects/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Serotonin/*metabolism MH - Serotonin Agents/*pharmacology EDAT- 2011/07/19 06:00 MHDA- 2011/12/30 06:00 CRDT- 2011/07/19 06:00 PHST- 2010/10/08 00:00 [received] PHST- 2011/06/24 00:00 [revised] PHST- 2011/06/29 00:00 [accepted] PHST- 2011/07/19 06:00 [entrez] PHST- 2011/07/19 06:00 [pubmed] PHST- 2011/12/30 06:00 [medline] AID - S1053-8119(11)00754-3 [pii] AID - 10.1016/j.neuroimage.2011.06.089 [doi] PST - ppublish SO - Neuroimage. 2011 Oct 1;58(3):885-94. doi: 10.1016/j.neuroimage.2011.06.089. Epub 2011 Jul 8.