Analysis of galanin and the galanin antagonist M40 on delayed non-matching-to-position performance in rats lesioned with the cholinergic immunotoxin 192 IgG-saporin.
Galanin is a 29-amino-acid neuropeptide that is overexpressed in Alzheimer's disease (AD) and impairs performance on rodent learning and memory tasks. M40, a peptidergic galanin receptor ligand, blocks galanin-induced impairments on delayed non-matching-to-position (DNMTP). The present experiments used the 192IgG-saporin lesion model of AD to evaluate the actions of galanin and M40 on DNMTP when cholinergic transmission was reduced. Hippocampal choline acetyltransferase levels were correlated with DNMTP choice accuracy in lesioned rats. Intracerebroventricular (icv) galanin reduced choice accuracy in both the lesioned and sham groups. M40 alone, either icv or intrahippocampal, did not affect choice accuracy in either group. These results suggest that excess galanin can produce further deficits in DNMTP performance in a lesion model of AD, but blocking endogenous galanin is not sufficient alone to improve performance in lesioned rats.
McDonald
M P
MP
Section on Behavioral Neuropharmacology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. mikemc@codon.nih.gov
Wenk
G L
GL
Crawley
J N
JN
D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001931:Brain Mapping; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019004:Galanin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D000922:Immunotoxins / Q000494:pharmacology*; D008297:Male; D011939:Mental Recall / Q000187:drug effects* / Q000502:physiology; D009699:N-Glycosyl Hydrolases; D009949:Orientation / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000502:physiology; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000502:physiology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; C079517:M40; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D054789:Ribosome Inactivating Proteins, Type 1; D019004:Galanin; D009699:N-Glycosyl Hydrolases; D000076985:Saporins