Differential role of serotonergic projections arising from the dorsal and median raphe nuclei in locomotor hyperactivity and prepulse inhibition.
While an involvement of brain serotonin systems in schizophrenia has been suggested by many studies, the relative role of different serotonergic projections in the brain remains unclear. We therefore examined the effects of selective brain serotonin depletion on psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, two animal models of aspects of schizophrenia. Pentobarbital-anesthetized (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically microinjected with 1 microl of a 5 microg/microl solution of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into either the dorsal or median raphe nucleus. At 2 weeks after the surgery, rats with dorsal raphe lesions did not show changes in psychotropic drug-induced locomotor hyperactivity, but displayed partial disruption of prepulse inhibition. In contrast, rats with median raphe lesions showed significant enhancement of phencyclidine-induced, but not amphetamine-induced locomotor hyperactivity and a marked disruption of prepulse inhibition. These results provide evidence for differential involvement of serotonergic projections in locomotor hyperactivity and prepulse inhibition. This study may help to explain the role of different serotonin projections in the brain in the pathophysiology of schizophrenia.
Kusljic
Snezana
S
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Parkville, Australia.
Copolov
David L
DL
van den Buuse
Maarten
M
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000161:Acoustic Stimulation; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins; D009433:Neural Inhibition / Q000187:drug effects*; D010622:Phencyclidine / Q000494:pharmacology; D011903:Raphe Nuclei / Q000293:injuries / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia; D018490:Serotonin Agents / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D013997:Time Factors
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D015116:5,7-Dihydroxytryptamine; D000661:Amphetamine; D010622:Phencyclidine