Possible role of citalopram and desipramine against sleep deprivation-induced anxiety like-behavior alterations and oxidative damage in mice.

Sleep is an essential physiological process for maintaining physical, mental, and emotional health. Sleep deprivation and associated disorders like depression and anxiety are one of the major problems now-days. The present study was designed to explore the neuroprotecitve effect of citalopram and desipramine on 72 hr sleep deprivation-induced behavioral alterations and oxidative damage in mice. Various behavioral tests (plus maze, zero maze, mirror chamber, actophotometer), body weight followed by oxidative parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were assessed. Treatment with citalopram (5 and 10 mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) for 5 days significantly improved locomotor activity, anti-anxiety like behavior in all paradigms tasks (mirror chamber, plus maze, zero maze) as compared to control (72 hr sleep-deprived). Biochemically, citalopram and desipramine treatment significantly restored depleted reduced glutathione, catalase activity, attenuated raised lipid peroxidation and nitrite level as compared to control (72 hr sleep-deprived) animals. Results of present study suggest that citalopram (5 and 10mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) have neuroprotective effect against sleep deprivation-induced behavior alteration and oxidative damage in mice.

Role of noradrenaline uptake inhibition and alpha-adrenoceptors in reperfusion ventricular arrhythmias in vivo and in vitro.

In view of the importance of sympathetic nervous system in the genesis of cardiac arrhythmias during reperfusion following coronary occlusion, the role of noradrenaline uptake inhibitor desipramine in the prevention of reperfusion arrhythmias was investigated in intact rabbit heart and isolated rat heart. For both the paradigms, ischaemia was produced by coronary artery ligation for 30 min followed by reperfusion for 60 min with drug administration at the time of reperfusion. Desipramine was used at three dose levels (0.2, 0.6 and 2.0 mg/kg) in the in vivo study while in vitro it was used at a concentration of 7 microM. Further, to investigate the status of adrenergic receptors during ischaemia and reperfusion, ischaemia was simulated by superfusing lactate physiological solution in isolated rabbit aortic strip preparation, which has well characterized alpha-receptors. Cumulative dose response curves (DRC) of selective alpha 1 agonist, phenylepherine (PE) were recorded during normal, ischaemic and reperfused conditions. Desipramine showed dose dependent anti-arrhythmic effect in vivo as well as in vitro. In intact heart studies desipramine offered protection against reperfusion arrhythmias in a dose related manner i.e. 50, 67.5 and 100% whereas in isolated studies, 50% protection was observed in the overall incidence of arrhythmias. DRC of PE shifted towards right during both ischaemia and reperfusion with a significant elevation of maximal response only during reperfusion.

Dopamine receptor mediated antidepressant action of B-HT 920 in mice.

Possible involvement of dopaminergic (DAergic) system in forced swimming-induced immobility (despair behaviour) was investigated in mice. B-HT 920 (0.05 and 0.1 mg/kg), a post-synaptic DAergic agonist, produced a dose dependent reduction in immobility period, which was sensitive to blockade by haloperidol (0.5 mg/kg) and sulpiride (100 mg/kg). This effect was also blocked by alpha 2 antagonist yohimbine (5 mg/kg). SKF 38393 (5 mg/kg), a D1-DA agonist potentiated the action of B-HT 920. Reserpinization (2 mg/kg, 24 hr prior) produced despair immobility in mice. When a low dose of B-HT 920 (0.05 mg/kg) was given to reserpinized animals, the duration of immobility period was further increased. But on the other hand, a higher dose (0.1 mg/kg) of it reduced reserpine-induced immobility. Desipramine (5 and 10 mg/kg), elicited a dose dependent reduction in the immobility period, which was sensitive to blockade by sulpiride (100 mg/kg). Desipramine (10 mg/kg) showed a diphasic response in combination with B-HT 920, i.e., a potentiation of the response due to a low dose of B-HT 920 (0.05 mg/kg) and an antagonism of the response due to a higher dose of B-HT 920 (0.1 mg/kg), respectively. SKF 38393 (5 mg/kg), potentiated the action of desipramine (5 mg/kg). SKF 38393 (5 mg/kg) further potentiated the action of desipramine (5 mg/kg) and B-HT 920 (0.05 mg/kg). These observations suggests that B-HT 920 reduces behavioural immobility by DAergic mechanism and desipramine also modulates D2-DA receptors in its anti-depressant action.

On the characterization of dopamine-induced contractile response of rat anococcygeus muscle preparation.

Presence of specific dopamine (DA) receptors and their characterization was attempted in rat anococcygeus muscle preparation. Dopamine (10(-6) M) and B-HT 920 (10(-6) M) produced concentration dependent contractions of the rat anococcygeus muscle preparation. The response of DA was shifted towards right in presence of haloperidol (10(-6) M; pA2 = 6.8) and sulpiride (10(-4) M) in a competitive manner. Alpha 2 antagonists yohimbine (10(-5) M) and idazoxan (10(-5) M) blocked the response to DA in a competitive manner, while alpha 1 antagonist prazosin (10(-5) M) completely blocked the response to DA. SCH 23390 (10(-5) M), a D1 DA antagonist potentiated the response to DA. Reserpinization (5 mg/kg, 24 hr prior) brought about a shift towards the right, and this response was similarly blocked by haloperidol, sulpiride and yohimbine without affecting the maximum response. Desipramine (10(-5) M) blocked the response of DA in a non-competitive manner. Pretreatment of animals with desipramine (10 mg/kg) followed by reserpine, brought about a reversal of action of reserpine. The response to B-HT 920 (10(-6) M), was blocked similarly by haloperidol and yohimbine. However, the effect of desipramine was more pronounced when compared to DA per se. SKF 38393, a D1 DA agonist, potentiated the response to B-HT 920. The findings suggest the presence of both D1 and D2 DA receptors in rat anococcygeus muscle and that DA also acts on adrenergic receptors to produce a contractile response of this muscle preparation.

Regional differences in the levels of biogenic amines and their metabolites in rat brain after tricyclic antidepressant treatments

Changes in the levels of biogenic amines in different brain regions and the cerebrospinal fluid in rats were measured after acute or chronic treatment with tricyclic antidepressants. After single or 3 weeks' treatment with imipramine or desipramine, blocks of tissues were obtained from seven regions of the brain (frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia nigra and cerebellum) immediately after collection of the cerebrospinal fluid (CSF) from the cisterna magna. The concentrations of biogenic amines and their metabolites (norepinephrine, epinephrine, dopamine, 5-hydroxytryptamine (5-HT), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA)) in brain tissues and the CSF were measured using the high performance liquid chromatography-electrochemical detection system (HPLC-ECD). Treatment with desipramine or imipramine caused major alterations in the concentrations of central norepinephrine or 5-HT and its metabolite, respectively. Brain regional responses were variable according to the kind of tricyclic antidepressants and the duration of treatment. It is noteworthy that chronic treatment with both desipramine and imipramine caused altered hippocampal concentrations of norepinephrine and/or 5-HT and its metabolites. Striatal DOPAC concentrations were also changed after acute or chronic treatment with both drugs. These results suggest that tricyclic antidepressants altered neurotransmission according to the brain region, and the hippocampal norepinephrine and 5-HT and/or the striatal dopamine may have a significant role for the expression of antidepressant action of tricyclic antidepressants.

Desipramine blocks stress-induced prolactin release in rats: role of central beta-2 adrenoceptors

The present study was designed to examine the relationship between beta-adrenoceptors and the enhanced, sustained prolactin secretion induced by immobilization stress in rats. Chronic administration of desipramine (15 mg kg**-1 day**-1, intraperitoneally) for 7 days, a procedure that desensitizes central beta-adrenoceptors, partially inhibits stress-induced prolactin release. Intracerebroventricular adminsitration of the beta-2 adrenoceptor agonist salbutamol (1 microng/rat) to rats pretreated with desipramine for 7 days, 15 min before immobilization, significantly relieved the inhibition by desipramine 5 and 10 min after the initiation of stress but the effect was not demonstrable after 20 and 40 min. We conclude that beta-2 adrenoceptors play a role in the control prolactin release in response to stress

Experimental evaluation of the antidepressant and neuroleptic activity of maprotiline.

Maprotiline, a tetracyclic antidepressant drug, was evaluated for antidepressant and neuroleptic activity. In antidepressant tests, maprotiline antagonized reserpine-induced ptosis in rats but, unlike the tricyclic antidepressants, was found to antagonize methamphetamine stereotypy in rats, to decrease the intensity of L-dopa induced behavioural syndrome in pargyline-pretreated mice and to be ineffective in intensifying the 5-HTP induced behavioural syndrome. In neuroleptic tests, maprotiline was found to, antagonize apomorphine-induced cage climbing behaviour, induce catalepsy, inhibit the CAR and traction response, decrease the spontaneous motor activity and exploratory behaviour, and to potentiate the hypnotic effect of pentobarbitone. Our results indicate that maprotiline exhibits a profile of activity which resembles the neuroleptics and most probably exerts post-synaptic striatal DA receptor blocking activity.