Margarita Saavedra

Desipramine restricts estral cycle oscillations in swimming.

1. Desipramine (DMI) is a tricyclic antidepressant which reduces the immobility in rats forced to swim; however, it is unknown whether estral cycle phases impinge on DMI actions on immobility in daily swimming tests during several weeks. 2. In female wistar rats, vaginal smears taken before testing defined four estral phases. Afterwards, the authors assessed the latency for the first period of immobility in five-min forced swim tests practiced on 21-day DMI (DMI group), 21-day washout saline given after a 21-day DMI treatment (washout-saline group), or non-treated rats (control group). 3. We observed a longer latency for the first period of immobility in proestrus-estrus from the control and washout-saline groups. The 21-day treatment with DMI (2.1 mg/kg i.p., once a day) significantly (p < 0.001) increased the latency by about 160% from control regardless of the estral cycle phase. 4. It is concluded that proestrus-estrus relates to increased struggling behavior. DMI enhances struggling behavior independently of hormonal state.

Lateral septal neuronal firing rate increases during proestrus-estrus in the rat

Neuronal activity of the lateral septal nucleus (LSN) is related to motivational and hedonic behavior. Even though some changes in mood and anxiety during proestrus and pregnancy have been reported, the possible changes in the neuronal activity of the LSN through the phases of the estrous cycle are unknown. In the present study we explored the neuronal activity from the LSN using glass micropipettes (NaCl 1 M, and Evans blue 2.5%; 3-8 Mohms in 30 urethane (1 g/kg) anesthetized Wistar rats. Analysis of data included a total of 88 single-unit extracellular recordings taken from the LSN during proestrus (n = 22), estrus (n = 23), diestrus (n = 22), and metestrus (n = 21). The highest values of firing rate were found in proestrus, and the lowest in metestrus, F(3,84) = 3.78, p < 0.01. During estrous cycles, in the phase characterized by high plasma levels of estradiol and progesterone, i.e., proestrus-estrus, the neurons from the dorsal aspect of the LSN fired at significantly (p < 0.05) higher frequencies, shorter first-order intervals and a lower coefficient of variation than those in the phase characterized by lower levels of estradiol and progesterone (metestrus-diestrus). In another group of rats (n = 12), immobility in the forced-swim test was assessed. Consistently, a longer latency (p < 0.05) for the first period of immobility and a nonsignificant trend to a lowered total time in immobility were found in proestrus and estrus. It is concluded that the higher firing rate in neurons from the dorsal aspect of the LSN during proestrus-estrus, may be associated with an increased motivation to escape from a stressful situation.

Participation of the lateral septal nuclei (LSN) in the antidepressant- like actions of progesterone in the forced swimming test (FST)

The possible participation of lateral septal nuclei (LSN) in the antidepressant-like actions of progesterone was evaluated. The effect of different concentrations of progesterone (0.001, 0.01 and 0.1 M) or saline solution injected directly into the LSN of ovariectomised rats was determined using the forced swimming test (FST). In addition, the temporal course of progesterone (0.1 M) antidepressant-like actions was compared with that of the classical antidepressant imipramine (0.1 M). Finally, in order to establish the possible participation of the GABA(A) receptor in the antidepressant-like action of progesterone, the effect of pre-treatment with the GABA(A) antagonist picrotoxin (0.125 mg/kg, i.p.) was evaluated. Intraseptally administered progesterone produced a concentration-dependent decrease in immobility behaviour but did not modify locomotor activity. These antidepressant-like actions lasted 4 h, while those of imipramine lasted 72 h. Finally, progesterone-induced anti-immobility effect could be blocked by the systemic injection of picrotoxin. Present results reveal that LSN play a role in the antidepressant-like actions of progesterone that appear to be mediated by the GABA(A) receptor.

Spontaneous firing rate of lateral septal neurons decreases after forced swimming test in Wistar rat

The systemic or local administration of diverse antidepressants increases the neuronal firing rate of the lateral septal nucleus (LSN), whereas some stressful situations decrease its firing rate; however, any long-lasting effect exerted by the forced swimming (FS) test (15-min pretest and 5-min test 24 h later) on the firing rate of the LSN is unknown. Therefore, single-unit extracellular recordings were obtained from the LSN neurons of control rats (Ctrl, n=6) and FS rats (n=10) 2 h after the last swimming session. In other rats, spontaneous firing rate of cortical neurons was recorded under the same experimental conditions. The firing rate of the LSN neurons of the animals in the FS group was significantly lower (9.2+/-1.7 spikes/10 s; P<.004, n=35) in comparison with the Ctrl group (21.1+/-3.4 spikes/10 s, n=22). The reduced firing rate in the LSN after swimming tests was both evident and generalized given that approximately 83% of the total recorded neurons from the FS group fired below the mean+/-1 S.D. rate obtained from the Ctrl group. Accordingly, the mean first-order interval of neuronal firing rate in the FS group (621.3+/-22.6 ms) was significantly greater (P<.05) than that observed in the Ctrl group (391.5+/-29.2 ms), but no significant differences were found in the variation coefficient of these two experimental groups, illustrating regularity of firing. Nonsignificant differences or even an opposite trend were observed in the firing rate of cortical neurons in the FS group (26.3+/-8.4 spikes/10 s) as compared with Ctrl group (15.4+/-1.1 spikes/10 s). Accordingly, no differences were found in the variation coefficient (FS 55.3+/-7.2%, Ctrl 55.8+/-3.6%) or average first-order interval (FS 417.8+/-71.8 ms, Ctrl 494.1+/-64.5 ms). We conclude that the FS test constitutes a situation whose capacity for inducing long-lasting despair is reflected in a reduction in the firing rate of LSN neurons as it occurs in situations of anxiety and fear, contrary to the actions of antidepressant drugs.

Intraaccumbens dopaminergic lesion suppresses desipramine effects in the forced swim test but not in the neuronal activity of lateral septal nucleus.

The nucleus accumbens (NAcc) function is related to locomotor activity, while the lateral septal nucleus (LSN) is related to the motivational aspects of behavior. Thus, a dopaminergic lesion of the NAcc blocks the antiimmobility effect of desipramine (DMI) and this tricyclic increases the firing rate of the LSN; however, it is unknown whether a relation exists between a dopaminergic lesion of the NAcc and the response of LSN neurons to DMI treatment. Therefore, we conducted a longitudinal study to further explore the participation of NAcc dopaminergic terminals in the immobility reduction exerted by DMI in the forced swim test and its relation to the firing rate of the LSN, at the same time exploring motor and motivational aspects of DMI-dopaminergic relationships in the animals. A dopaminergic lesion was bilaterally produced by 6-hydroxydopamine (6-OHDA) injection into the NAcc of adult ovariectomized Wistar rats pretreated with DMI (25 mg/kg ip, 30 min before lesion to protect NA terminals but to destroy DA endings). Treatments with DMI or saline began 24 h after stereotaxic surgery. The results showed that DMI once a day during 9 days (10 mg/kg) reduced immobility in the forced swim test in the sham-lesion group (P<.02); however, in the dopaminergic lesion group submitted to DMI treatment, immobility remained at control level in agreement with other reports. DMI increased the firing rate of the LSN (P<.001) independently of the 6-OHDA lesion. In conclusion, the dopaminergic terminals of the NAcc seem to be essential for the motor manifestation associated with motivation induced by DMI in the forced swim test, given that the antiimmobility actions of DMI are blocked after a dopaminergic NAcc lesion; however, the effect on the firing rate of LSN neurons is still present.

The combination of several antidepressants is not synergistic on the firing of lateral septal neurons in the rat.

1. Three kinds of antidepressants (clomipramine, sleep deprivation, and electroconvulsive shock) increase the firing rate in the lateral septal neurons of the rat. 2. The acute combination of these treatments, however, did not produce added effects on firing rate of lateral septal neurons in the rat. 3. 24 hours of sleep deprivation blocked the actions of a single electroconvulsive shock. 4. It is concluded that the firstly applied treatment modifies the receptors sensitivity from the very beginning, thus blocking the action of a second treatment.