Phencyclidine exacerbates attentional deficits in a neurodevelopmental rat model of schizophrenia.
Schizophrenia is characterized by severe abnormalities in cognition, including disordered attention. In the rat, neonatal ventral hippocampal (NVH) lesions induce behavioral abnormalities at adulthood thought to simulate some aspects of the symptomatology of schizophrenia. Here, we compared the effects of NVH and adult ventral hippocampal (AVH) lesions on attentional performance as assessed by the five-choice serial reaction time task (5-CSRTT). NVH-lesioned rats were slower to acquire the task than AVH-lesioned and control animals. When training was complete, NVH- and AVH-lesioned animals exhibited stable but disrupted performance under standard conditions, thus emphasizing an implication of VH in visual attentional processes. Variations in task parameters induced a significantly greater disruption in NVH- and AVH-lesioned groups as compared to controls. NVH-lesioned rats were also hyper-responsive to the disruptive effects of a high dose of phencyclidine (PCP) (3 mg/kg). In contrast, amphetamine (0.4-0.8 mg/kg) had a similar effect in control and VH-lesioned rats. Thus, NVH-lesioned rats were impaired in the acquisition of stable performance in the 5-CSRTT, and were hypersensitive to the cognitive-impairing effects of PCP.
Le Pen
Gwenaëlle
G
INSERM-EMI 0117, Centre Paul Broca, Paris, France. lepen@broca.inserm.fr
Grottick
Andrew J
AJ
Higgins
Guy A
GA
Moreau
Jean-Luc
JL
D000375:Aging; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology*; D001522:Behavior, Animal; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D002755:Choice Behavior / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000293:injuries / Q000473:pathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012559:Schizophrenia / Q000150:complications* / Q000503:physiopathology
D000697:Central Nervous System Stimulants; D000661:Amphetamine; D010622:Phencyclidine