RESUMO
Urinary excretion of neopterins (N) and biopterins (B) was measured in 48 patients with depression before and after treatment with placebo, antidepressants, or electroconvulsive therapy (ECT), and in 26 healthy control subjects. Patients prior to and after treatment had a significantly greater neopterin/biopterin (N:B) ratio than control subjects. There was a significant correlation between N:B ratios and the severity of depression and plasma cortisol. As a raised N:B ratio implies failure to convert neopterin to biopterin, it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate-limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive illness.
Assuntos
Antidepressivos/uso terapêutico , Biopterinas/análogos & derivados , Biopterinas/urina , Transtorno Depressivo/terapia , Eletroconvulsoterapia , Adulto , Idoso , Amitriptilina/efeitos adversos , Amitriptilina/uso terapêutico , Antidepressivos/efeitos adversos , Ensaios Clínicos como Assunto , Transtorno Depressivo/psicologia , Transtorno Depressivo/urina , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Neopterina , Piperoxano/efeitos adversos , Piperoxano/análogos & derivados , Piperoxano/uso terapêutico , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Pirrolidinonas/efeitos adversos , Pirrolidinonas/uso terapêutico , Valores de Referência , RolipramAssuntos
Inibidores de Adenilil Ciclases , Amitriptilina/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Piperoxano/análogos & derivados , Pirróis/uso terapêutico , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Adulto , Idoso , Plaquetas/efeitos dos fármacos , Plaquetas/enzimologia , Transtorno Depressivo/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperoxano/uso terapêuticoRESUMO
This experiment demonstrated that behavioral depression produced by exposure of rats to strong uncontrollable shocks could be reversed by infusion of the alpha-2 adrenergic agonist clonidine into the region of the locus coeruleus (LC). A 20-min infusion, through bilateral cannulae, into the locus coeruleus of clonidine, piperoxane (alpha-2 antagonist) or inactive vehicle (0.85% saline), was given beginning 70 min after the animals were removed from the stress situation. The dose and volume of drug given in the infusion (0.16 microgram/microliter, 0.1 microliter/min) had been previously shown to produce effects specific to the locus coeruleus (Weiss, Simson, Hoffman, Ambrose, Cooper and Webster, 1986; Neuropharmacology 25: 367-384). At the conclusion of the infusion, active behavior of animals was measured in a 15-min swim test. Results showed that stressed animals infused with vehicle exhibited significantly less active behavior in the swim test than did non-stressed animals infused with vehicle, thereby showing the usual behavioral depression seen after exposure to an uncontrollable stress. Stressed animals infused with clonidine showed no difference in active behavior in comparison to non-stressed animals infused with vehicle and showed significantly more activity than did the stressed animals infused with vehicle. Stressed animals infused with piperoxane showed no significant difference in activity in comparison to the stressed animals infused with vehicle and were significantly less active than either the non-stressed animals infused with vehicle or the stressed animals infused with clonidine. Thus, infusion into the locus coeruleus of the alpha-2 agonist clonidine, but not the alpha-2 antagonist piperoxane, eliminated behavioral depression.(ABSTRACT TRUNCATED AT 250 WORDS)
