Nancy E. Córdoba

Reactivity of amphetamine in perinatally undernourished rats: Behavioral and neurochemical correlates

Adult rats deprived at perinatal age and then rehabilitated on balanced chow were treated with a multiple amphetamine (AMPH) schedule (2 mg/kg/48 hr) and submitted, on days of injections, to an open-field test. Throughout 11 sessions, deprived rats showed a progressive increase of locomotor activity as compared with controls. Stereotyped activity evaluated during the AMPH treatment did not differ between control and deprived animals. No differences were detected in basal values of the dopaminergic function measured in naive control and deprived animals. By the end of the multiple AMPH treatment, a reduction of striatal DA and DOPAC levels together with a lower apparent DA turnover rate was detected in deprived animals. Besides, DA receptor binding was significantly increased in striatum from deprived rats as compared with controls. These results demonstrate that a repeated AMPH treatment, that was unable to alter the normal behavior of control rats, produced in early undernourished animals a progressive sensitization to AMPH effects, in addition to significant changes in the striatal dopaminergic function.

Decreased reactivity to the anticonflict effect of diazepam in perinatally undernourished rats

Offspring of rats were submitted to a protein deprivation dietary treatment from the third week of gestation until 50 days of age, and later nutritionally rehabilitated for at least 90 days. In the punished lever-pressing conflict test, undernourished animals exhibited a decreased reactivity to the anticonflict effect of a 3 mg/kg dose of diazepam as compared to control animals. This decreased reactivity to diazepam in a shock-induced conflict test indicates that functional alterations in the GABAergic transmission might contribute to the state of hypersensitivity to stressful or aversive situations present in undernourished animals.

Lack of tolerance to the anxiolytic effect of diazepam and pentobarbital following chronic administration in perinatally undernourished rats

Adult female rats, undernourished at perinatal age, were evaluated for anxiolytic action in the plus-maze test after acute and chronic administration of diazepam (DZP) and pentobarbital (PTB). Deprived (D) rats chronically treated with vehicle showed an increased anxiety as compared with control (C) animals. A single intraperitoneal (i.p.) administration of DZP (1 mg/kg) or PTB (7.5 mg/kg) produced similar anticonflict effect in both C and D rats. Tolerance to the anxiolytic effect of DZP and PBT developed in C rats after a 15-day administration schedule, whereas no tolerance was observed in D animals. Drug disposition was not altered after chronic treatment either in C or in D rats. Gamma-aminobutyric acid (GABA)-mediated chloride uptake in microsacs of cerebral cortex of naive D rats was decreased as compared with naive C rats. After chronic DZP administration (1 mg/kg/day i.p. for 15 days), GABA-mediated 36Cl- influx in brain cortex microsacs of C rats did not change; however, GABA efficacy was increased in microsacs of D animals. In addition, chronic DZP treatment induced GABA-benzodiazepine uncoupling in brain cortex of C rats, but not in D animals, as assessed by chloride uptake in microsacs. Chronic PTB treatment (7.5 or 30 mg/kg/day i.p. for 15 days) did not modify GABA stimulation or GABA-PTB interaction in cortical microsacs of C or D rats.

Perinatally protein-deprived rats and reactivity to anxiolytic drugs in the plus-maze test: An animal model for screening antipanic agents?

Adult rats submitted to a protein deprivation schedule at perinatal age (from 14th day of fetal life until 50 days of age) and then recovered on balanced chow (D rats) were assayed in the elevated plus-maze test for anticonflict effects of diazepam and drugs with therapeutic efficacy in panic disorders as compared with controls (C rats). Diazepam and alprazolam showed a similar anticonflict effect in D rats than in C rats. In contrast, buspirone, which was ineffective in C rats at a wide dosage range, showed a significant anticonflict effect on D rats at 0.3 mg/kg. Neither propranolol, desipramine, nor phenelzine treatment (10 mg/kg/day during 3-7 days) induced anticonflict effect in C rats. Conversely, these treatments fostered a significant and selective anxiolytic effect on D rats. Such results underscore long-lasting alterations caused by early undernutrition, namely, changes in reactivity to the drugs assayed. In addition, perinatally deprived rats may represent a useful animal model for studying potential antipanic agents.

Perinatal undernutrition reduced ethanol intake preference in adult recovered rats

Adult female rats submitted to a protein deprivation schedule at perinatal age (from 14th day of fetal life until 50 days of age) were tested for alcohol intake in a preference test. When compared with control animals, experimental rats exhibited higher overall fluid intake. Nevertheless, in terms of ethanol preference these subjects evidenced lower preference to this drug. A test for assessing ethanol olfactory preference did not show any differences between control and experimental rats in basal conditions. However, after repeated exposure to alcohol, deprived rats showed an aversion to ethanol odor, while controls evidenced the opposite effect, i.e., heightened preference. Possible differences to the aversive effects of ethanol between control and experimental animals were assayed by means of two taste aversion tests, by associating alcohol to sucrose or NaCl. No differences were detected between both groups of rats. These results demonstrate that early undernutrition reduces ethanol preference in a free choice situation. Such an effect could be due, at least partially, to odor aversion developed by repeated exposure.

Reduced tolerance to certain pharmacological effects of ethanol after chronic administration in perinatally undernourished rats.

We have previously reported that recovered adult rats undernourished at perinatal age failed to develop tolerance to the anticonflict effect of ethanol after chronic ethanol administration (1 g/kg/day during 30 days) (4). To further study the extent of this finding, we examined the effect of a similar chronic ethanol treatment on the hypothermic and anticonvulsant effects of ethanol in perinatally deprived rats. Hypoalgesic activity was assessed in ethanol treated rats during 15 days. After chronic ethanol treatment, a similar development of tolerance to the hypothermic effect of ethanol was observed in control and deprived rats. However, tolerance to the anticonvulsant and hypoalgesic effect of ethanol was significantly reduced in deprived as compared with control animals. Thus, early undernutrition differentially affects the development of tolerance elicited by chronic ethanol administration.

Gangliosides enhance the anti-immobility response elicited by several antidepressant treatments in mice

Ganglioside pretreatment enhanced the anti-immobility effect induced in the forced swim test after a chronic treatment with desipramine, mianserin, clomipramine, nialamide or repeated electroconvulsive shock in mice. Gangliosides, which had no effect per se, showed a clear dose-response relationship in enhancing the anti-immobility effect of desipramine. These results suggest that, regardless of their mechanisms of action, gangliosides facilitate the behavioral response of several antidepressant treatments.