Decreased GABA B receptors in helpless rats: reversal by tricyclic antidepressants.
Recently, sufficient evidence has accumulated to suggest that a central GABAergic dysfunction may be primarily related to the physiopathology of affective disorders and that antidepressant mechanisms have an intrinsic GABAergic component. In depressed patients GABA levels are reported to be low in the cerebral spinal fluid and plasma, and GABA synthesis is decreased in some brain areas, including the frontal cortex. GABA mimetics exhibit antidepressant-like actions in behavioral models in the olfactory bulbectomized rat and in the learned helplessness paradigm. In the olfactory bulbectomized rat, GABA B receptors are down regulated in the frontal cortex and in the learned helplessness paradigm, GABA release is diminished in the hippocampus. These decreases are reversed by antidepressants in parallel with their behavioral activities. In this study, data obtained indicate that in the learned helplessness paradigm, GABA B receptors are decreased in the frontal cortex and this decrease is reversed by imipramine and desipramine (16 mg/kg/day) in animals which are considered to be 'responders' to antidepressant treatments.
Martin
P
P
Département de Pharmacologie, Faculté de Médecine Pitié-Salpêtrière, Paris.
Pichat
P
P
Massol
J
J
Soubrié
P
P
Lloyd
K G
KG
Puech
A J
AJ
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects; D006380:Helplessness, Learned; D006624:Hippocampus / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D000929:Antidepressive Agents, Tricyclic; D011963:Receptors, GABA-A; D007099:Imipramine; D003891:Desipramine