Essential role of D1 but not D2 receptors in methamphetamine-induced impairment of long-term potentiation in hippocampal-prefrontal cortex pathway.
Methamphetamine (MA) abuse induces deficits in cognitive performance that are related to dysfunction of the prefrontal cortex (PFC). The medial portion of the prefrontal cortex (mPFC) in rats that is crucial for cognitive function has been shown to undergo long-term potentiation (LTP) in the projections from the hippocampus. However, no study has been performed to evaluate the influence of MA on synaptic plasticity in the hippocampal-mPFC pathways. In the present experiments, we investigated the effects of repeated MA administration on hippocampal-mPFC LTP, together with MA-induced stereotyped behaviors. Repeated MA administration produced behavioral sensitization and LTP impairment in the hippocampal-mPFC pathways. The MA-induced impairment of hippocampal-mPFC LTP was prevented by the pretreatment of dopamine 1 (D1) but not dopamine 2 (D2) receptor antagonists, while D1 and D2 receptor antagonists attenuated the MA-induced stereotyped behaviors. These findings suggest that D1 receptors are crucial for the MA-induced deterioration of synaptic plasticity in the hippocampal-mPFC circuits. Impairment of LTP associated with D1 receptor dysfunction may underlie cognitive deficits in MA-dependent subjects.
Ishikawa
Akinori
A
Department of Neuroscience, Yamaguchi University School of Medicine,1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan. akinori@yamaguchi-u.ac.jp
Kadota
Tomoko
T
Kadota
Ken
K
Matsumura
Hideki
H
Nakamura
Shoji
S
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D020891:Raclopride; D008694:Methamphetamine