Differential involvement of 5-HT projections within the amygdala in prepulse inhibition but not in psychotomimetic drug-induced hyperlocomotion.
While there is abundant evidence for a role of 5-HT and the amygdala in anxiety and depression, the role of 5-HT in this brain region in schizophrenia is less well understood. We therefore examined the effects of local 5-HT depletion in the amygdala on psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition, two animal model of aspects of schizophrenia. Pentobarbital-anaesthetized (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically micro-injected with 0.5 microl of a 5 microg/mul solution of the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into either the basolateral (BLA) or central nucleus of amygdala (CeN). Two weeks after the surgery, rats with BLA lesions did not show changes in either psychotomimetic drug-induced locomotor hyperactivity or prepulse inhibition. In contrast, rats with CeN lesions showed significant disruption of prepulse inhibition, but no changes in psychotomimetic drug-induced locomotor hyperactivity. Neurochemical analysis and autoradiographic labelling of 5-HT transporter sites showed that a good degree of anatomical selectivity was obtained. Following administration of 5,7-DHT into the amygdala, the concentration of 5-HT was significantly reduced. Similarly, 5-HT transporter autoradiographs showed differential and selective lesions of 5-HT innervation in targeted subregions of the amygdala. These results provide evidence for differential involvement of 5-HT projections within the amygdala in prepulse inhibition but not locomotor hyperactivity. Thus, the present study supports the view that 5-HT in the amygdala may be involved in aspects of schizophrenia and a target for antipsychotic drug action.
Kusljic
Snezana
S
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Vic. 3052, Australia.
van den Buuse
Maarten
M
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000161:Acoustic Stimulation; D000679:Amygdala / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism
D015116:5,7-Dihydroxytryptamine; D015283:Citalopram; D003913:Dextroamphetamine; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D010622:Phencyclidine; D012701:Serotonin; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors