Clomipramine increases the responsiveness of raphe-cortical neurons in the rat.

The cerebral cortex of the rat possesses 5-HT1A receptor subtype; however, whether the activation of this receptor by dorsal raphe nucleus stimulation produces a similar action on neuronal cortical firing as antidepressants acting on serotonin (5-HT) function is unknown. Single-unit extracellular recordings were obtained from parietal cortex in rats in which dorsal raphe nucleus or cerebellar peduncle was stimulated. Results compared groups long-term treated with clomipramine (1.25 mg/kg i.p., twice a day, during 30 days) or saline (0.15 ml i.p., twice a day, during 30 days). Amplitude of traces, firing rate, and response to treatment with clomipramine proved to be different between cortical neurons responding to dorsal raphe nucleus or cerebellar peduncle stimulation. Clomipramine increased a long-lasting cortical suppression of firing elicited by dorsal raphe nucleus stimulation. Obtained data suggests that the responses of nearby cortical neurons containing different kinds of 5-HT receptors may relate to the involved pathways and that clomipramine seems to act on 5-HT1A receptor subtype.

Clomipramine enhances the excitatory actions of dorsal raphe nucleus stimulation in lateral septal neurons in the rat.

Clomipramine is a serotonin reuptake blocker which produces an increased rate of firing in lateral septal neurons of the rat. However, it is unknown whether the response of dorsal raphe nucleus stimulation on the firing rate of the lateral septal neurons is modified by clomipramine treatment. Two programs of stimulation were employed. In the first, iterative stimulation (0.3 Hz, 1 ms, 0.1 mA) produced a complex pattern of response in which activation responses predominated, and clomipramine increased the duration and the firing rate of afterdischarge. In the second program a short train of pulses (300 Hz, 500 ms, 0.1 ms) was applied to the dorsal raphe nucleus. Clomipramine increased both the duration and the frequency of firing with respect to the saline-treated group. The present data show that dorsal raphe nucleus stimulation produces a long-lasting increase in the firing rate of lateral septal neurons which is enhanced by clomipramine. Since clomipramine applied to the septal area produces a decrease in firing, it is concluded that actions taken by clomipramine on raphe nuclei produce a disinhibitory process in the lateral septal neurons.

Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions.

In cerebral cortex and lateral septal nuclei different serotonergic receptor subtypes coexist, thus a different action on neuronal firing may be expected depending on the receptor activated. Dorsal raphe nucleus stimulation produced an increased rate of firing in cortical layer V, and in lateral septal nuclei. However, firing rate in cortical layer VI remained unchanged after stimulating the dorsal raphe nucleus. Clomipramine is a tricyclic which exerts its main actions on serotonergic receptors, and long-term treatment with this antidepressant produced a selective increased firing rate in lateral septal neurons, but not in cortical neurons. From an electrophysiological point of view, it is concluded that the excitatory actions on firing rate elicited by dorsal raphe nucleus stimulation or clomipramine treatment are mediated by 5-HT2 receptor subtype activation which is likely to be acting as a 5-HT1A modulator in such places where both receptor subtypes coexist.