8-OH-DPAT-induced effects on prepulse inhibition: pre- vs. post-synaptic 5-HT1A receptor activation.
Prepulse inhibition (PPI) is a measure of sensorimotor gating that is deficient in schizophrenia. In rats, administration of the serotonin-1A (5-HT1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), causes a disruption of PPI. It is unclear whether this effect is due to the activation of pre- or post-synaptic 5-HT1A receptors, however pre-synaptic receptors located in the dorsal raphe nucleus (DRN) may play a role. Our previous research showed that castrated rats have a reduced sensitivity to 8-OH-DPAT-induced disruptions of PPI. Therefore, in , male Sprague-Dawley rats were sham-operated or castrated and micro-injected with 8-OH-DPAT directly into the DRN. In , male rats were sham-operated or received a selective serotonergic, 5,7-dihydroxytryptamine lesion of the DRN. 8-OH-DPAT was injected subcutaneously in these rats. In both sham-operated and castrated rats, a micro-injection of 8-OH-DPAT into the DRN did not disrupt PPI. Instead, in castrated rats, 8-OH-DPAT treatment tended to increase PPI. A DRN lesion caused a significant reduction in 5-HT content in the frontal cortex (70% reduction), striatum (69%) and ventral hippocampus (76%). In both sham-operated and DRN-lesioned rats, systemic 8-OH-DPAT significantly disrupted PPI. Taken together, these data suggest that the disruption of PPI observed in rats with systemic 8-OH-DPAT treatment is predominantly due to an activation of post-synaptic, rather than pre-synaptic, 5-HT1A receptors.
Gogos
Andrea
A
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Parkville, VIC 3052, Australia. agogos@mhri.edu.au
Kusljic
Snezana
S
van den Buuse
Maarten
M
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000161:Acoustic Stimulation; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009919:Orchiectomy; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D018490:Serotonin Agents / Q000633:toxicity; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D058825:Serotonin 5-HT1 Receptor Agonists; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin