Selective antagonism of medial prefrontal cortex D4 receptors decreases fear-related behaviour in rats.
It is well known that the mesolimbocortical dopamine pathway is highly active during periods of stress and fear. However, very little research has directly examined how dopamine receptors in this pathway influence fear-related behaviour. The present study examined the effects of selective antagonism of D(4), D(1) and D(2) dopamine receptors of the medial prefrontal cortex (MPFC) on rats' fear behaviour in the elevated plus-maze and the shock-probe burying tests. The results demonstrated that bilateral intra-MPFC infusions of the highly selective D(4) antagonist, L-745 870 (0.2, 1 or 10 nmol/0.5 microL), increased the percentage of open-arm entries and open-arm time in the elevated plus-maze test (1 nmol/0.5 microL), and decreased the duration of burying in the shock-probe test (0.2 or 1 nmol/0.5 microL). Furthermore, none of the doses of the D(4) antagonist affected measures of general activity or pain sensitivity. Intra-MPFC infusions of the D(1) antagonist, SCH-23390 (0.2 or 1 nmol/0.5 microL), or the D(2) antagonist, remoxipride (0.2, 1 or 10 nmol/0.5 microL), had no significant behavioural effects in either test. Taken together, these findings suggest that MPFC D(4) receptors may play an important role in the mediation of fear-related behaviour.
Shah
Akeel A
AA
Department of Psychology, University of Alberta, Edmonton, AB, Canada. aashah@ualberta.ca
Sjovold
Travis
T
Treit
Dallas
D
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D018492:Dopamine Antagonists / Q000008:administration & dosage; D065127:Dopamine D2 Receptor Antagonists; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493601:Drd4 protein, rat; D050638:Receptors, Dopamine D4