RESUMO
This study evaluated the antidepressant-like effect of insulin compared to sertraline and a combination of insulin and sertraline in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats submitted to the forced swim test (FST). Male Wistar rats were daily treated for 21 days with insulin (1 or 2 IU/kg, i.p.), with the selective serotonin reuptake inhibitor (SSRI), sertraline (10 mg/kg, i.p.), or with a combination of insulin (1 or 2 IU/kg, i.p.) and sertraline (10 mg/kg, i.p.) and submitted to the FST. We also evaluated the water and food intake, urine volume and weight gain of the rats. Rats treated with STZ showed impaired glucose tolerance. Chronic treatment with sertraline showed an antidepressant-like effect in non-diabetic and diabetic rats. Furthermore, sertraline promoted lower weight gain in diabetic rats. Insulin reduced the immobility behaviour in T2DM rats with impaired glucose tolerance. In conclusion, our results showed that insulin has an antidepressant-like effect comparable to that of sertraline. Sertraline is effective as an antidepressant and reduces weight gain, which reinforces its superiority over other SSRIs in the treatment of major depression disorder in patients with T2DM.
Assuntos
Antidepressivos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Insulina/farmacologia , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Intolerância à Glucose/tratamento farmacológico , Masculino , Ratos , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sertralina/farmacologia , Aumento de Peso/efeitos dos fármacosRESUMO
A wealth of evidence indicates that the activation of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal grey matter (dPAG) inhibits escape, a panic-related defensive behaviour. Results that were previously obtained with the elevated T-maze test of anxiety/panic suggest that 5-HT1A and µ-opioid receptors in this midbrain area work together to regulate this response. To investigate the generality of this finding, we assessed whether the same cooperative mechanism is engaged when escape is evoked by a different aversive stimulus electrical stimulation of the dPAG. Administration of the µ-receptor blocker CTOP into the dPAG did not change the escape threshold, but microinjection of the µ-receptor agonist DAMGO (0.3 and 0.5 nmol) or the 5-HT1A receptor agonist 8-OHDPAT (1.6 nmol) increased this index, indicating a panicolytic-like effect. Pretreatment with CTOP antagonised the anti-escape effect of 8-OHDPAT. Additionally, combined administration of subeffective doses of DAMGO and 8-OHDPAT increased the escape threshold, indicating drug synergism. Therefore, regardless of the aversive nature of the stimulus, µ-opioid and 5-HT1A receptors cooperatively act to regulate escape behaviour. A better comprehension of this mechanism might allow for new therapeutic strategies for panic disorder.
Assuntos
Reação de Fuga/fisiologia , Pânico/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Receptor 5-HT1A de Serotonina/fisiologia , Receptores Opioides mu/fisiologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/antagonistas & inibidores , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Estimulação Elétrica , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Reação de Fuga/efeitos dos fármacos , Masculino , Microinjeções , Pânico/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Ratos , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Receptor 5-HT2A de Serotonina , Receptores Opioides mu/antagonistas & inibidores , Somatostatina/administração & dosagem , Somatostatina/análogos & derivados , Somatostatina/farmacologiaRESUMO
This study investigated the effects of repeatedly administration of an aqueous fraction of Paullinia cupana Kunth, Sapindaceae (guaraná) seeds (8 mg/kg) on rats submitted to the elevated T-maze, model of generalized anxiety and panic disorders. The selective serotonin reuptake inhibitor paroxetine (3 mg/kg), was used as a positive control. To evaluate possible neurotransmissions involvement, ineffective doses of metergoline (3 mg/kg - non-selective serotonin receptor antagonist), sulpiride (20 mg/kg - non-selective dopaminergic receptor antagonist) or ketamine (0.125 mg/kg - non-selective glutamate receptor antagonist) were acutely administered in association with the aqueous fraction of P. cupana. Both aqueous fraction and paroxetine decrease the inhibitory avoidance latencies of the elevated T-maze, indicating anxiolytic effect and increased one-way escape latencies from the open arm of the elevated T-maze, indicating a panicolytic effect. The pre-treatment with metergoline, sulpiride and ketamine blocked the anxiolytic effect of aqueous fraction. The panicolytic effect of aqueous fraction was blocked by both metergoline and sulpiride. These results show that the serotonergic, dopaminergic and glutamatergic neurotransmission systems are involved in anxiolytic effect promoted by aqueous fraction, whereas only the serotonergic and the dopaminergic neurotransmission systems are involved in the panicolytic effect promoted by aqueous fraction of P. cupana. The effects produced by paroxetine, were blocked only by metergoline, validating this experimental procedure.