Dopamine D1/D5 receptor activation fails to initiate an activity-independent late-phase LTP in rat hippocampus.
The role of dopamine in the hippocampus remains poorly defined. Numerous studies have suggested that it acts as a neuromodulator of late-phase long-term potentiation (L-LTP) in CA1, while other reports controversially indicate that D1/D5 receptor (D1/D5R) activation may directly initiate activity-independent LTP. We have further investigated this putative role of dopamine in area CA1 in rat hippocampal slices using field potential recording techniques. Application of the dopamine D1/D5 receptor agonists SKF 38393 and 6-bromo-APB at 100 microM for 20 min did not induce an activity-independent L-LTP. Varying the incubation conditions still did not permit either SKF 38393 or an alternative D1/D5R agonist, 6-chloro-PB, to induce L-LTP. To further determine if intracellular mechanisms, which may act to limit the expression of LTP, were preventing D1/D5R-induced L-LTP expression, we inhibited protein phosphatase 1 activity by reducing cyclin-dependent kinase 5 (cdk5) inhibition of inhibitor 1. Inhibition of cdk5 by roscovitine (10 microM, 40 min) did not facilitate the ability of SKF 38393 to induce L-LTP in CA1. Biochemical experiments confirmed that the concentration of agonist used significantly elevated intracellular cAMP levels, suggesting that effective D1/D5R activation was achieved. Furthermore, coactivation with NMDA receptors (NMDAR) resulted in a synergistic increase in cAMP. These findings demonstrate that D1/D5R activation in CA1 initiates intracellular second messenger accumulation, but that this is insufficient to induce an activity-independent L-LTP.
Mockett
Bruce G
BG
Department of Psychology, University of Otago, P.O. Box 56, Dunedin 9001, New Zealand. mockettb@psy.otago.ac.nz
Brooks
Wendy M
WM
Tate
Warren P
WP
Abraham
Wickliffe C
WC
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D050641:Receptors, Dopamine D5; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D015259:Dopamine Agents; C493607:Drd5 protein, rat; D018690:Excitatory Amino Acid Agonists; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D050641:Receptors, Dopamine D5; D016202:N-Methylaspartate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP