Assessment of auditory sensory processing in a neurodevelopmental animal model of schizophrenia--gating of auditory-evoked potentials and prepulse inhibition.
The use of translational approaches to validate animal models is needed for the development of treatments that can effectively alleviate cognitive impairments associated with schizophrenia, which are unsuccessfully treated by the current available therapies. Deficits in pre-attentive stages of sensory information processing seen in schizophrenia patients, can be assessed by highly homologues methods in both humans and rodents, evident by the prepulse inhibition (PPI) of the auditory startle response and the P50 (termed P1 here) suppression paradigms. Treatment with the NMDA receptor antagonist PCP on postnatal days 7, 9, and 11 reliably induce cognitive impairments resembling those presented by schizophrenia patients. Here we evaluate the potential of early postnatal PCP (20mg/kg) treatment in Lister Hooded rats to induce post-pubertal deficits in PPI and changes, such as reduced gating, in the P1 suppression paradigm in the EEG. The results indicate that early postnatal PCP treatment to rats leads to a reduction in PPI of the acoustic startle response. Furthermore, treated animals were assessed in the P1 suppression paradigm and produced significant changes in auditory-evoked potentials (AEP), specifically by an increased P1 amplitude and reduced P2 (P200 in humans) gating. However, the treatment neither disrupted normal P1 gating nor reduced N1 (N100 in humans) amplitude, representing two phenomena that are usually found to be disturbed in schizophrenia. In conclusion, the current findings confirm measures of early information processing to show high resemblance between rodents and humans, and indicate that early postnatal PCP-treated rats show deficits in pre-attentional processing, which are distinct from those observed in schizophrenia patients.
Broberg
Brian Villumsen
BV
Department of In vivo Neuropharmacology, H. Lundbeck A/S, Ottiliavej 9, Valby, Denmark.
Oranje
Bob
B
Glenthøj
Birte Yding
BY
Fejgin
Kim
K
Plath
Niels
N
Bastlund
Jesper Frank
JF
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D010622:Phencyclidine; D051381:Rats; D011919:Rats, Inbred Strains; D012559:Schizophrenia / Q000503:physiopathology*; D055139:Sensory Gating / Q000502:physiology*
D010622:Phencyclidine