Effect of amitriptyline on blood glucose level in rabbits.

Effect of single graded doses of amitriptyline (4, 8 and 16, mg/kg, p.o.) were observed on blood glucose level in 18 h fasted albino rabbits. All the doses of Amitriptyline produced significant hyperglycemia at 4 h, which attained a peak at 24 h with 16 mg/kg dose and appears to be due to blockade of the uptake of monominergic transmitters across the axoplasmic membrane, It (16 mg/kg) also produced glucose intolerance during early hours probably due to interference with gastrin function.

Effect of mianserin on blood glucose level in rabbits.

Blood glucose level was estimated in 18 h fasted albino rabbits following acute feeding of graded doses of mianserin. Mianserin (6.0 mg/kg) produced a gradually increasing hyperglycemic effect which became significant (P < 0.01) at 10 h and onwards. This appears to be due to increased turnover and release of noradrenaline by the drug. The same dose of mianserin also produced glucose intolerance during early hours probably by interfering with gastrin functions.

Effect of acute & chronic imipramine treatment on glucose homeostasis.

Single dose of imipramine (IMI) produced significant (P less than 0.05) hyperglycemia in rabbits, the effect peaking at 1 h. The hyperglycemic response was less marked in rabbits which were chronically pretreated with IMI for 4 wk. Simultaneous administration of insulin, oral glucose or adrenaline with single doses of IMI resulted in an enhancement of usual hypoglycemic/hyperglycemic responses of these agents. However, when these drugs were administered in chronically IMI fed animals there was complete reversion of the enhancement. Daily administration of adrenaline for further 6 days with IMI feeding in the chronically IMI treated rabbits, led to enhancement in the hyperglycemic response to adrenaline (P less than 0.001). In contrast, similar administration of insulin resulted in reduced hypoglycemia. Further, glucose feeding with IMI plus adrenaline or insulin in these animals did not result in any significant alteration in blood glucose level (BGL), as compared to oral glucose plus single doses of adrenaline or insulin. GTT done on the day next to drug treatment in rabbits chronically pretreated with IMI and than with IMI plus insulin, produced an enhanced hyperglycemic response, as compared with the control group (P less than 0.01). These observations indicate that acute (but not chronic) treatment with IMI not only produces a rise in BGL per se but also enhances the response to other agents which affect glucose homeostasis.

Modulation of glucose homeostasis by doxepin.

Blood glucose level (BGL) was estimated up to 4 h (3 h in case of GTT) in 18-h fasted albino rabbits following acute and chronic (one month) feeding of doxepin and thereafter for another 8 days together with either insulin or glibenclamide or adrenaline. A single dose of doxepin produced significant hypoglycemia which peaked at 4 h and lasted up to 10 h. On chronic doxepin feeding there was complete attenuation of initial hypoglycemia on the 7th and 14th days, culminating into frank hyperglycemia on the 21st day. However, there was complete recovery on the 29th day exhibiting tolerance to initial hypo-as well as delayed hyperglycemia. Similarly, glucose intolerance was accentuated on the 8th day followed by a gradual recovery on the 15th and 22nd days, culminating in disappearance of glucose intolerance on the 30th day. The hypoglycemic effect of insulin was markedly potentiated in chronically doxepin fed animals which was further enhanced on continuing administration of both agents. Profound hypoglycemia was observed during GTT in such animals. The hyperglycemic effect of adrenaline was enhanced in chronically doxepin fed animals, which may be due to TCA induced enhancement of the response of exogenous adrenaline. Suppression of this hyperglycemia with continued administration of both drugs seems to be due to subsensitivity of alpha 2-adrenoceptors. Additive hyperglycemia was observed during GTT in such animals.

Effect of electroconvulsions on glucose homeostasis in rabbits.

Acute electroconvulsions (ECS) produced hyperglycemic response in rabbits which peaked at 30 min and recovered within 4 h. This hyperglycemic response to acute ECS was significantly more marked in rabbits which were chronically pretreated with ECS. The hyperglycemic responses to acute ECS and oral glucose were additive in nature. Daily administration of adrenaline in chronically ECS pretreated rabbits further enhanced the hyperglycemic response to acute ECS. The hyperglycemic response to oral glucose and parenteral adrenaline were significantly more marked in such rabbits. GTT done on the day next to ECS, in rabbits chronically pretreated with ECS and then with ECS plus adrenaline produced enhanced hyperglycemic response. These results indicate that repetitive ECS disturbs glucose homeostasis.

Effect of electroconvulsions on leucocyte counts.

Acute electroconvulsions (EC) induced polymorphonuclear leucocytosis with relative lymphopenia in rabbits. On daily EC challenge there was no tolerance to this response but the response was blocked by propranolol. Repeated daily administration of exogenous adrenaline or EC challenge increased basal total leucocyte and polymorph but decreased the lymphocyte counts. It is suggested that repeated exposure to exogenous adrenaline or endogenous adrenaline (through EC) somehow sensitizes the system responsible for the release of polymorphs from the bone marrow.