Further characterization of the effect of the prototypical antidepressant imipramine on the microstructure of licking for sucrose

Abstract

We previously reported that treatment with the prototypical antidepressant imipramine induced a dose-dependent reduction of the ingestion of a 10% sucrose solution, due to reduction of the licking burst number, thus suggesting reduced motivation and/or increased satiation. Importantly, the experimental sessions were performed in an alternate order, either 1-h or 24-h after imipramine administration. The observation that imipramine effect was more pronounced in the “1-h after-treatment” sessions, i.e. at the time of the brain drug Cmax, led us to suggest that it was likely related to brain drug levels at testing time. However, such an experimental design does not allow to rule out the alternative possibility that the observed effect might be due to post-session administration, as previously observed with memantine. To determine whether imipramine-induced decrease of sucrose ingestion could be observed even in absence of post-session administration, we examined the effect of a daily 22 day treatment with imipramine (5, 10 and 20 mg/kg). In the first half of the treatment period all behavioural tests were performed 1-h after administration. In the second half of the treatment period, tests were performed alternatively either 1-h or 24-h after imipramine administration. The results confirm that imipramine reduces sucrose ingestion due to a reduction of the licking burst number. Most importantly, these results demonstrate that this effect does not require imipramine post-session administration, since it was present before the beginning of post-session administrations. This supports the interpretation of the reduction of sucrose ingestion as a consequence of reduced motivation and/or increased satiation. Thus, these findings, taken together with the results of our previous study, might be relevant in explaining the effects of imipramine in models of drug-seeking and in body weight gain reduction in rats, but not in accounting for the antidepressant therapeutic effect. At variance with the results of our previous study, an increase in burst size was present in the first half of the treatment period, which might be interpreted as a prohedonic effect and/or as a compensatory effect.

Dopamine, activation of ingestion and evaluation of response efficacy: a focus on the within-session time-course of licking burst number

“…In the course of a chronic treatment with imipramine (D’Aquila and Galistu 2021 ), an increased burst size was observed with imipramine (10 mg/kg) in sessions run 1 h after a daily treatment, possibly suggesting an increased hedonic response to sucrose. However, this result is inconsistent with the result of a parallel study (D’Aquila and Galistu 2020 ).…”

“…an effect mimicking the effect of reward devaluation on operant responding. It should be stressed that the few published studies focusing on a detailed analysis of the within-session burst number time-course were conducted in our laboratory (D’Aquila 2010 , 2020 ; D’Aquila and Galistu 2017 , 2021 ; D’Aquila et al 2019 ; Galistu and D’Aquila 2013 , 2020 ; Galistu et al 2011 ). As we shall see, a few pieces of evidence from other laboratories might provide support to the interpretative framework suggested here about the functional meaning of this parameter (Frisina and Sclafani 2002 ; Robles and Johnson 2017 ).…”

Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment

“…Imipramine (10,11-dihydro-N,N-dimethyl-5H-dibenz[b,f]azepine-5-propanamine) is a prototype of tricyclic antidepressants [344], structurally similar to phenothiazines [345]. Imipramine reduces the uptake of norepinephrine and serotonin by neurons by blocking Na + -dependent serotonin and norepinephrine transporters [346], which increases their concentration in the synaptic cleft and alleviates symptoms of depression [347,348].…”

Combinatorial Regimen of Carbamazepine and Imipramine Exhibits Synergism against Grandmal Epilepsy in Rats: Inhibition of Pro-Inflammatory Cytokines and PI3K/Akt/mTOR Signaling Pathway

“…Imipramine (IMI; dibenzazepine-derivative) is a prototype of tricyclic antidepressants (TCAs) [16], structurally related to phenothiazines [17]. IMI reduces the neuronal uptake of norepinephrine (NE) and serotonin (5-HT) by blocking the Na + dependent 5-HT and NE transporters [18], which increases the concentration of NE and 5-HT at the synaptic cleft (thereby modulating the protein kinase signaling and changes in neuro-transmission) and relieving the depressive symptoms [19].…”