The effect of dopamine receptor blockade in the rodent nucleus accumbens on local field potential oscillations and motor activity in response to ketamine.
Altered functioning of the nucleus accumbens (NAc) has been implicated in the psychotomimetic actions of NMDA receptor (NMDAR) antagonists and the pathophysiology of schizophrenia. We have shown previously that NMDAR antagonists enhance the power of high-frequency oscillations (HFO) in the NAc in a dose-dependent manner, as well as increase locomotor activity. Systemic administration of NMDAR antagonists is known to increase the release of dopamine in the NAc and dopamine antagonists can reduce ketamine-induced hyperactivity. In this study, we examined the effect of 0.5 μl intra-NAc infusion of 3.2 μg SCH23390 (D1 antagonist), 10 μg raclopride (D2 antagonist) and saline on ketamine-induced changes in motor and oscillatory activity. We found that local blockade of D1 receptors attenuated ketamine-induced increases in motor activity and blockade of D2 receptors produced a much weaker effect, with respect to saline-infused control groups. In contrast, none of the antagonists, infused separately or together, significantly modified the power or dominant frequency of ketamine-induced increases in HFO, but changes in delta and theta frequency bands were observed. Together, these findings suggest, that, in contrast to delta and theta frequency bands, the generation of ketamine enhanced-HFO in the NAc is not causally related to locomotor activation and occurs largely independently of local changes in dopamine receptor activation.
Matulewicz
Pawel
P
Laboratory of the Limbic System, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093 Warsaw, Poland.
Kasicki
Stefan
S
Hunt
Mark Jeremy
MJ
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D001703:Biophysics; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D004569:Electroencephalography / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism*; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D011954:Receptors, Dopamine; C534628:SCH 23390; D020891:Raclopride; D007649:Ketamine