Enhancement of performance in multiple learning tasks by corticotropin-releasing factor-binding protein ligand inhibitors.
Evidence favors a role for corticotropin-releasing factor (CRF) in learning and memory processes. A binding protein (CRF-BP) with the ability to inactivate CRF provides a novel target to modulate endogenous levels of CRF. The present studies employed three measures of information processing in rats in order to examine the impact of CRF system activation resulting from administration of CRF-BP ligand inhibitors, which increase levels of "free CRF." Acquisition of a visual discrimination paradigm and retention of a inhibitory avoidance task were dose dependently facilitated by central administration of a CRF-BP ligand inhibitor. CRF-BP ligand inhibitor treatment also improved performance in an active avoidance paradigm in aged animals. No nonspecific anorexic effects of the active dose of CRF-BP ligand inhibitor were detected in a food intake test. Moreover, the magnitude of in vivo efficacy of the CRF-BP ligand inhibitor peptide in producing a mild increase in motor activity was dissociated from that of a postsynaptic CRF receptor agonist that exerted robust and long-lasting activity increases. Thus, CRF-BP ligand inhibitors appear to elicit generalized learning enhancement effects without mimicking the robust nonspecific behavioral actions of a CRF receptor agonist.
Heinrichs
S C
SC
Neurocrine Biosciences, Inc., San Diego, CA 92121, USA. sheinrichs@neurocrine.com
Vale
E A
EA
Lapsansky
J
J
Behan
D P
DP
McClure
L V
LV
Ling
N
N
De Souza
E B
EB
Schulteis
G
G
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism*; D004193:Discrimination Learning / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017208:Rats, Wistar
D002352:Carrier Proteins; C067133:corticotropin releasing factor-binding protein; D003346:Corticotropin-Releasing Hormone