The role of hippocampal dopamine receptors in prepulse inhibition.
Although it has long been realized that the hippocampal formation receives a projection from the midbrain dopaminergic cell groups and contains mRNA for all five dopamine receptors, the functional role of this dopaminergic projection has not been studied so far. The present study aimed to investigate the role of dopamine receptors in the dorsal CA1 area of the hippocampus in prepulse inhibition. The results show that local application of amphetamine reduced prepulse inhibition without affecting the baseline startle amplitude. This effect of amphetamine could be reversed by coadministration of the D1 antagonist SCH23390. Moreover, local application of the D1 agonist SKF81297 also disrupted prepulse inhibition without altering basal startle amplitude. These data clearly suggest that the hippocampal D1 receptor plays an important role in prepulse inhibition. The effects of amphetamine could not be reversed by coadministration of the D2 antagonist sulpiride. Interestingly, the D2/3 agonist quinpirole did reduce prepulse inhibition, again without affecting basal startle amplitude. Because quinpirole has a much higher affinity for the D3 receptor than does sulpiride, it is suggested that the D3 receptor might be involved in this effect.
Ellenbroek
Bart A
BA
Department of Psychoneuropharmacology, PO Box 9101, 6500 HB Nijmegen, The Netherlands. A.Ellenbroek@pnf.kun.nl
Lubbers
Luuk J
LJ
Cools
Alexander R
AR
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism
D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D000661:Amphetamine; D004298:Dopamine