Dopaminergic modulation of hippocampus-dependent learning: blockade of hippocampal D1-class receptors during learning impairs 1-trial place memory at a 30-min retention delay.
Consistent with the requirement of D1-class dopamine receptors for the induction of late (>3 h) hippocampal long-term potentiation (LTP), hippocampus-dependent 1-trial memory at long retention delays (>6 h) requires hippocampal D1-class receptors during learning. Hippocampal D1-class receptors also modulate the induction and magnitude of early LTP (<1-3 h). However, a corresponding modulation of the formation of hippocampus-dependent early (<1 h) memory remains to be revealed. We addressed this conceptually important issue, using a novel modification of the watermaze delayed-matching-to-place (DMP) test with an improved measure of hippocampus-dependent 1-trial place memory. On the DMP test, rats learn the novel location of a hidden escape platform on trial 1 of every day, so that 1-trial place memory can be measured on trial 2. Our new task modification includes the measurement of search preference for the correct location on trial 2 - a very sensitive index of hippocampus-dependent place memory. We examined the effects of hippocampal D1-class receptor blockade or stimulation during learning on memory at a 30-min retention delay. Bilateral hippocampal infusion of the D1-class receptor antagonist SCH23390 (1 or 5 μg/1 μl/side) before trial 1 dose-dependently impaired such early memory: rats infused with the higher dose showed reduced search preference for the correct location and took longer paths to reach this location. Infusion of the D1-class partial agonist SKF38393 (1 or 5 μg/1 μl/side) did not affect measures of 1-trial place memory. Our data reveal a behavioural correlate of the dopaminergic modulation of early LTP, thereby supporting the close correspondence between hippocampal LTP and hippocampus-dependent learning.
School of Psychology, University of Nottingham, University Park, Nottingham NG7 2RD, UK. marie.pezze@nottingham.ac.uk
Marie
M
Pezze
Tobias
T
Bast
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D057967:Infusions, Intraventricular; D007858:Learning / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013037:Spatial Behavior / Q000187:drug effects; D013997:Time Factors
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1