Antagonism at Serotonin 5-Ht2a Receptors Modulates Functional Activity of Fronto-Hippocampal

Supplementary information

ANTAGONISM AT SEROTONIN 5-HT2A RECEPTORS MODULATES FUNCTIONAL ACTIVITY OF FRONTO-HIPPOCAMPAL CIRCUIT

Psychopharmacology

Alessandro Gozzi1 Valerio Crestan2 Giuliano Turrini2 Marcel Clemens1#Angelo Bifone1

1Biology, 2Laboratory Animal Science, Neurosciences CEDD, GlaxoSmithKline Medicines Research Centre, Verona, Italy;

#Present AddressOsservatorio Astronomico di Padova,Padova

Corresponding author:

Alessandro Gozzi

Neuroimaging, GSK Neurosciences CEDD

Fleming 4, 37100 VERONA (ITALY)

Phone + 39 0458219233

FAX + 39 0458218073

Table 1

Mean group weights and arterial blood gases measurements

Group / Weight(g) / paCO2 pre / paCO2post / paO2pre / paO2 post
#1 / 322±5 / 35±1 / 42±2 / 151±13 / 115±10
#2 / 329±8 / 38±2 / 42±3 / 151±17 / 114±9
#3 / 341±12 / 35±1 / 42±2 / 116±13 / 114±7
#4 / 273±4 / 36±1 / 44±2 / 159±6 / 123±11
#5 / 342±6 / 31±2 / 36±4 / 165±13 / 155±11
#6 / 345±6 / 33±2 / 41±3 / 170±11 / 150±10
#7 / 328±7 / 40±2 / 36±2 / 199±9 / 207±4

Abbreviations: PaCO2 - partial pressure of arterial CO2; PaO2 - partial pressure of arterial O2; values were recorded prior to and at the end of phMRI timeseries, respectively. Values expressed as mmHg and presented as mean ± SEM

Supplementary Figure 1

Input function used for the GLM analysis of phMRI time series (see Methods). The regressor was identified using wavelet-cluster analysis as described in (Schwarz et al., 2006b)

Supplementary Figure 2

rCBV timecourse following PCP injection in representative brain structures. PCP was administered at time 0. Baseline data were obtained in animals pretreated and challenged with vehicle (saline, group 5). Data are plotted as mean±SEM within each group. Veh-PCP: group 3, M100907 (0.5 mg/kg) – PCP: group 4, Veh-Veh: group 5. [PFC: medial prefrontal cortex; VHc: ventral hippocampus; DLTh: dorsolateral thalamus, S1Ctx: primary somatosensory cortex].

Supplementary Figure 3

rCBV timecourse following PCP injection in representative brain structures. PCP was administered at time 0. Baseline data were obtained in animals pretreated and challenged with vehicle (saline, group 7). Data are plotted as mean±SEM within each group. Veh-PCP: group 5, SCH23390(0.1 mg/kg i.p.) – PCP: group 6, Veh-Veh: group 7. [PFC: medial prefrontal cortex; VHc: ventral hippocampus; DLTh: dorsolateral thalamus, S1Ctx: primary somatosensory cortex].

Supplementary Figure 4

Effect of pretreatment with M100907 (1.5 mg/kg, group 2) or vehicle (group 1) per se on rCBV baseline in four representative brain regions. M100907 or vehicle (saline) were administered at time 0. Data are plotted as mean±SEM within each group.[PFC: medial prefrontal cortex; VHc: ventral hippocampus; DLTh: dorsolateral thalamus, S1Ctx: primary somatosensory cortex].

Supplementary Figure 5

Effect of pretreatment with M100907 (0.5 mg/kg, group 4) or vehicle (group 3) per se on rCBV baseline in four representative brain regions. M100907 or vehicle (saline) were administered at time 0. Data are plotted as mean±SEM within each group.[PFC: medial prefrontal cortex; VHc: ventral hippocampus; DLTh: dorsolateral thalamus, S1Ctx: primary somatosensory cortex].

Supplementary Figure 6

Effect of pretreatment with SCH23390 (0.1 mg/kg, group 6) or vehicle (group 5) per se on rCBV baseline in four representative brain regions. SCH23390 or vehicle (saline) were administered at time 0. Data are plotted as mean±SEM within each group.[PFC: medial prefrontal cortex; VHc: ventral hippocampus; DLTh: dorsolateral thalamus, S1Ctx: primary somatosensory cortex].