TY - JOUR
T1 - Dissociating scopolamine-induced disrupted and persistent latent inhibition
T2 - Stage-dependent effects of glycine and physostigmine
AU - Barak, Segev
AU - Weiner, Ina
N1 - Funding Information:
Acknowledgments This research was supported by the Israel Science Foundation (grant No. 1234/07) and by the Josef Sagol Fellowship Program in Brain Studies at Tel-Aviv University (SB).
PY - 2010/4
Y1 - 2010/4
N2 - Rationale Latent inhibition (LI) is the poorer conditioning to a stimulus seen when conditioning is preceded by repeated non-reinforced pre-exposure to the stimulus. LI indexes the ability to ignore irrelevant stimuli and is used extensively to model attentional impairments in schizophrenia. We showed that the pro-psychotic muscarinic antagonist scopolamine can produce LI disruption or LI persistence depending on dose and stage of administration: low doses disrupt LI acting in the pre-exposure stage of the LI procedure, whereas higher dose produces abnormally persistent LI via action in the conditioning stage. The two LI abnormalities show distinct response to antipsychotic drugs (APDs), with LI disruption, but not LI persistence, reversed by APDs. Objectives The objective of this study is to show that both LI abnormalities will be reversed by the cognitive enhancers, glycine and physostigmine, in a stage-specific manner, reversing each abnormality via the stage at which it is induced by scopolamine. Methods LI was measured in a conditioned emotional response procedure. Scopolamine, physostigmine, and glycine were administered in pre-exposure and/or in conditioning. Results Scopolamine (0.15 mg/kg)-induced disrupted LI was reversed by glycine (800 mg/kg) and physostigmine (0.15 mg/kg) via action in pre-exposure, whereas scopolamine (1.5 mg/kg)-induced persistent LI was reversed by these compounds via action in conditioning. In addition, glycine reversed scopolamine-induced disrupted LI via action in conditioning. Finally, glycine failed to reverse amphetamine-induced disrupted LI. Conclusions These results extend the pharmacological differentiation between scopolamine-induced disrupted and persistent LI and indicate that the scopolamine LI model may have a unique capacity to discriminate between typical APDs, atypical APDs, and cognitive enhancers.
AB - Rationale Latent inhibition (LI) is the poorer conditioning to a stimulus seen when conditioning is preceded by repeated non-reinforced pre-exposure to the stimulus. LI indexes the ability to ignore irrelevant stimuli and is used extensively to model attentional impairments in schizophrenia. We showed that the pro-psychotic muscarinic antagonist scopolamine can produce LI disruption or LI persistence depending on dose and stage of administration: low doses disrupt LI acting in the pre-exposure stage of the LI procedure, whereas higher dose produces abnormally persistent LI via action in the conditioning stage. The two LI abnormalities show distinct response to antipsychotic drugs (APDs), with LI disruption, but not LI persistence, reversed by APDs. Objectives The objective of this study is to show that both LI abnormalities will be reversed by the cognitive enhancers, glycine and physostigmine, in a stage-specific manner, reversing each abnormality via the stage at which it is induced by scopolamine. Methods LI was measured in a conditioned emotional response procedure. Scopolamine, physostigmine, and glycine were administered in pre-exposure and/or in conditioning. Results Scopolamine (0.15 mg/kg)-induced disrupted LI was reversed by glycine (800 mg/kg) and physostigmine (0.15 mg/kg) via action in pre-exposure, whereas scopolamine (1.5 mg/kg)-induced persistent LI was reversed by these compounds via action in conditioning. In addition, glycine reversed scopolamine-induced disrupted LI via action in conditioning. Finally, glycine failed to reverse amphetamine-induced disrupted LI. Conclusions These results extend the pharmacological differentiation between scopolamine-induced disrupted and persistent LI and indicate that the scopolamine LI model may have a unique capacity to discriminate between typical APDs, atypical APDs, and cognitive enhancers.
KW - Acetylcholinesterase inhibitors
KW - Animal model
KW - Attention
KW - Glycine
KW - Latent inhibition
KW - Muscarinic
KW - Schizophrenia
KW - Scopolamine
UR - http://www.scopus.com/inward/record.url?scp=77952766114&partnerID=8YFLogxK
U2 - 10.1007/s00213-010-1785-z
DO - 10.1007/s00213-010-1785-z
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AN - SCOPUS:77952766114
SN - 0033-3158
VL - 209
SP - 175
EP - 184
JO - Psychopharmacology
JF - Psychopharmacology
IS - 2
ER -