Repeated administration of imipramine modifies GABAergic transmission in rat frontal cortex.

Alterations in the functions of brain gamma-aminobutyric acid (GABA) inhibitory system and a distortion in the balance between excitatory and inhibitory synaptic transmission have been hypothesized to be possible causes of mood disorders. Experimental evidence points to modifications of GABAergic transmission as a result of prolonged treatment with antidepressant drugs, however, the influence of the tricyclic antidepressant imipramine on inhibitory synaptic transmission in the rat cerebral cortex has not yet been investigated. Therefore, in the present study the effects of single and repeated administration of imipramine were evaluated ex vivo in slices of the rat frontal cortex using electrophysiological approach.

Imipramine counteracts corticosterone-induced enhancement of glutamatergic transmission and impairment of long-term potentiation in the rat frontal cortex.

The effects of corticosterone administration lasting for 7 and 21 days were studied ex vivo in rat frontal cortex slices prepared 48 h after the last dose of the hormone. In slices originating from corticosterone-treated animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Corticosterone administration also resulted in an increase of the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons.

The GABA B receptor agonist CGP44532 and the positive modulator GS39783 reverse some behavioural changes related to positive syndromes of psychosis in mice.

Background And Purpose: An important role of GABAergic neurotransmission in schizophrenia was proposed a long time ago, but there is limited data to support this hypothesis. In the present study we decided to investigate GABA(B) receptor ligands in animal models predictive for the antipsychotic activity of drugs. The GABA(B) receptor antagonists CGP51176 and CGP36742, agonist CGP44532 and positive allosteric modulator GS39783 were studied.

Increased excitability of cortical neurons induced by associative learning: an ex vivo study.

In adult mice, classical conditioning in which whisker stimulation is paired with an electric shock to the tail results in a decrease in the frequency of head movements, induces expansion of the cortical representation of stimulated vibrissae and enhances inhibitory synaptic interactions within the 'trained' barrels. We investigated whether such a simple associative learning paradigm also induced changes in neuronal excitability. Using whole-cell recordings from ex vivo slices of the barrel cortex we found that layer IV excitatory cells located in the cortical representation of the 'trained' row of vibrissae had a higher frequency of spikes recorded at threshold potential than neurons from the 'untrained' row and than cells from control animals.

Repeated administration of imipramine attenuates glutamatergic transmission in rat frontal cortex.

The effects of repeated administration of a tricyclic antidepressant, imipramine, lasting 14 days (10 mg/kg p.o., twice daily), were studied ex vivo in rat frontal cortex slices prepared 48 h after last dose of the drug.