Blockade by diazepam of conditioned fear-induced activation of rat mesoprefrontal dopamine neurons.
The effect of diazepam on activation of the mesoprefrontal dopamine (DA) system by an emotional stress model without direct physical stimuli was examined. Environmental stimuli previously paired with inescapable footshock (conditioned fear) elicited increases in levels of the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the medial prefrontal cortex and of plasma corticosterone in rats. The increases in both levels were blocked by pretreatment with diazepam (5 mg/kg, IP); such blocking effects were reversed by Ro 15-1788 (15 mg/kg, IP), the benzodiazepine (BZD) receptor antagonist. These data suggest that diazepam can block activation of mesoprefrontal DA neurons as well as hypothalamo-pituitary-adrenocortical system elicited by the conditioned fear paradigm. This action appears to be a specific action of BZDs mediated through BZD receptors. We suggest that blocking effects of BZDs on the hyperactivity of the mesoprefrontal DA neurons may be one neural mechanism of their anxiolytic actions.
Ida
Y
Y
Department of Pharmacology, Kurume University School of Medicine, Japan.
Tsuda
A
A
Sueyoshi
K
K
Shirao
I
I
Tanaka
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003213:Conditioning, Psychological / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D003975:Diazepam / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005239:Fear / Q000502:physiology*; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological / Q000503:physiopathology*
D015102:3,4-Dihydroxyphenylacetic Acid; D005442:Flumazenil; D003975:Diazepam; D004298:Dopamine; D003345:Corticosterone