Effect Of Chronic Desipramine Research Articles

Chronic Treatment With Desipramine Induces an Estrous Cycle-Dependent Anxiolytic-Like Action in the Burying Behavior, But Not in the Elevated Plus-Maze Test

FERNÁNDEZ-GUASTI, A., L. MARTÍNEZ-MOTA, E. ESTRADA-CAMARENA, C. M. CONTRERAS AND C. LÓPEZ-RUBALCAVA. Chronic treatment with desipramine induces an estrous cycle dependent anxiolytic-like action in the burying behavior, but not in the elevated plus-maze test. PHARMACOL BIOCHEM BEHAV 63(1) 13–20, 1999.—The effect of chronic desipramine (DMI, 2.5 mg/kg × 21–26 days) treatment in female rats in two anxiety paradigms was assessed: the burying behavior (BB) and the elevated plus-maze (EPM) tests. In the BB test DMI produced a significant decrease in burying in ovariectomized rats, an effect considered as anxiolytic-like. In cycling females, DMI also reduced the cumulative BB most notably in proestrus rats. However, in diestrus rats no anxiolytic-like actions were observed. In addition, DMI increased BB latencies in proestrus and estrus rats. In the EPM test, DMI produced anxiolytic-like actions only in ovariectomized rats, while no significant actions were found in cycling females. Finally, the chronic treatment with DMI produced a general reduction in the ambulatory behavior of rats in all estrous cycle phases. Results are discussed on the basis of the differences between both anxiety paradigms and the probable relationship between the steroids secreted during proestrus and chronic DMI treatment.

Effects of chronic desipramine on waiting behaviour for a food reward in olfactory bulbectomized rats

The effects of olfactory bulbectomy (OB) on the 'waiting behaviour' of rats for a food reward in a T-maze, as well as the effect of chronic treatment with desipramine (7.5 mg/kg, i.p. x 14 days) prior to and throughout testing was assessed. In the T-maze, the time spent in locating a reward was longer in OB rats during the first phase of the food reward test. However, all groups chose the larger reward in at least 80% of trials by day 5 of test. Upon imposition of a delay in acquisition of the larger reward (phase 2), sham-operated rats chose the larger reward in correspondingly fewer trials until, by day 5, only 13% (control sham group) and 29% (desipramine-treated sham group) of trials were for the larger but delayed reward. By contrast, both OB rat groups continued to choose the larger but delayed reward throughout phase 2 in the majority of trials. The typical behavioural hyperactivity of OB rats in the 'open field' apparatus was attenuated by chronic administration of DMI. The results suggest that the OB rat has a deficit in food-motivated behaviour and appears to have reduced adaptation of this learned response when the conditions of the test are altered. Chronic desipramine treatment did not attenuate this effect.

Schedule-induced oral self-administration of cocaine and ethanol solutions: lack of effect of chronic desipramine

Groups of rats drinking either solutions of cocaine HCl (0.16 mg/ml), ethanol (2.5% v/v), or water, drank excessive, equivalent volumes in daily, 3-h sessions of food-pellet delivery under a fixed-time 1-min (FT 1-min) schedule. During single-session exposures to pellet-delivery schedules using longer inter-pellet values (FT 3- or 5-min probe sessions), the cocaine and ethanol groups, but not the water group, drank greater ml/pellet amounts, confirming previous research. Inasmuch as enhanced ml/pellet intake during the greater FT probes correlated with the abuse potential of the drinking solution in previous research, the effect of chronic desipramine HCl (2 mg/kg, i.p. daily) on this enhanced intake response was determined. For all groups, chronic desipramine treatment (2 mg/kg was judged to be the maximum dose free of non-specific, suppressive effects) affected neither FT 1-min schedule-induced polydipsia nor did it affect the enhanced ingestional response to the greater FT probes for the cocaine and ethanol groups. Chronic administration of desipramine may have therapeutic efficacy in treating cocaine abuse only in subjects attempting to refrain from cocaine who are aided in their passage through a withdrawal phase by desipramine.

Reduced metabolism and turnover rates of rat brain dopamine, norepinephrine and serotonin by chronic desipramine and zimelidine treatments

As part of of an ongoing effort to compare changes in whole body turnover of catecholamines and serptonin in man with those induced by antidepressants in the rat brain, we have evaluated the chronic effects of desipramine (DMI) and zimelidine (ZMI) on brain catecholamines and serotonin in the rat. The amines and metabolites measured include norepinephrine (NE), dopamine (DA) and their metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenlacetic acid (DOPAC) and homovanillic acid (HVA). Three brain areas were analysed; the hypothalamus, caudate nucleus and frontal cortex. Chronic DMI and ZMI reduced hypothalamic MHPG and caudate nucleus DA metabolites, in particular HVA. Both drugs reduced NE and DA turnover rates (estimated after α-methyl-p-tyrosine injection) and the rate of MHPG formation in the hypothalamus (estimated after pargyline treatment). They did not change NE turnover rate, but reduced DA turnover rate and rate of HVA formation in the caudate nucleus. Chronic DMI but not ZMI reduced DOPAC rate of formation in the caudate nucleus. Apparently changes in DA turnover and metabolism produced by these antidepressants are better related to changes in HVA than DOPAC concentrations. Similar to their influence on hypothalamic and caudate nucleus catecholamines, both chronic DMI and ZMI produced changes in serotonin concentration in the caudate nucleus and frontal cortex serotonin that suggest a reduction in its turnover rate and metabolism. The reduction in NE turnover in hypothalamus is consistent with the effects of chronic DMI and ZMI on whole body NE turnover observed in man. In conclusion, DMI and ZMI affect all three major monoamine neurotransmitter (NE, DA and serotonin) systems in ways that suggest reduced presynaptic neuronal activity. The influence of these antidepressants on caudate nucleus DA calls for the reassessment of the role of DA in the mechanism of action of antidepressants in other brain dopaminergic regions.