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Reversal of antidepressant-induced dopaminergic behavioural supersensitivity after long-term chronic imipramine withdrawal.
Eur J Pharmacol. 2003 Jan 01; 458(1-2):129-34.EJ

Abstract

Chronic antidepressant treatments enhance dopaminergic neurotransmission in the mesolimbic dopamine system. We suggested that this potentiation might underlie both the antidepressant therapeutic effect and the antidepressant-induced switch from depression to mania, which in turn, might be involved in the development of rapid cycling in bipolar patients. In this study, we investigated the changes occurring in the sensitivity of the mesolimbic dopamine system up to 40 days after antidepressant withdrawal. Male Sprague-Dawley rats were treated for 3 weeks with imipramine (20 mg/kg) and tested for motor activity 24 h, 12, 33 and 40 days after treatment withdrawal. Ambulatory activity and rearing counts were recorded after challenge with the dopamine D2-like receptor agonist quinpirole (0.15 mg/kg). Imipramine increased the motor response to quinpirole, 24 h after treatment discontinuation. No relevant differences between the groups were found after 12 and 33 days. After 40 days, a decreased level of rearing was observed in the group treated with imipramine. These results show a reversal of the imipramine-induced dopaminergic supersensitivity after 40 days of chronic imipramine withdrawal and suggest that the mood-switches observed in bipolar patients following antidepressant treatment and subsequent withdrawal, i.e. mania followed by rebound depression, might depend upon parallel changes in the mesolimbic dopamine system sensitivity.

Authors+Show Affiliations

Dipartimento di Scienze del Farmaco, Università di Sassari, via Muroni 23/a, 07100, Sassari, Italy. dsfpaolo@ssmain.uniss.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12498916

Citation

D'Aquila, Paolo S., et al. "Reversal of Antidepressant-induced Dopaminergic Behavioural Supersensitivity After Long-term Chronic Imipramine Withdrawal." European Journal of Pharmacology, vol. 458, no. 1-2, 2003, pp. 129-34.
D'Aquila PS, Peana AT, Panin F, et al. Reversal of antidepressant-induced dopaminergic behavioural supersensitivity after long-term chronic imipramine withdrawal. Eur J Pharmacol. 2003;458(1-2):129-34.
D'Aquila, P. S., Peana, A. T., Panin, F., Grixoni, C., Cossu, M., & Serra, G. (2003). Reversal of antidepressant-induced dopaminergic behavioural supersensitivity after long-term chronic imipramine withdrawal. European Journal of Pharmacology, 458(1-2), 129-34.
D'Aquila PS, et al. Reversal of Antidepressant-induced Dopaminergic Behavioural Supersensitivity After Long-term Chronic Imipramine Withdrawal. Eur J Pharmacol. 2003 Jan 1;458(1-2):129-34. PubMed PMID: 12498916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of antidepressant-induced dopaminergic behavioural supersensitivity after long-term chronic imipramine withdrawal. AU - D'Aquila,Paolo S, AU - Peana,Alessandra T, AU - Panin,Francesca, AU - Grixoni,Chiara, AU - Cossu,Maria, AU - Serra,Gino, PY - 2002/12/25/pubmed PY - 2003/5/17/medline PY - 2002/12/25/entrez SP - 129 EP - 34 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 458 IS - 1-2 N2 - Chronic antidepressant treatments enhance dopaminergic neurotransmission in the mesolimbic dopamine system. We suggested that this potentiation might underlie both the antidepressant therapeutic effect and the antidepressant-induced switch from depression to mania, which in turn, might be involved in the development of rapid cycling in bipolar patients. In this study, we investigated the changes occurring in the sensitivity of the mesolimbic dopamine system up to 40 days after antidepressant withdrawal. Male Sprague-Dawley rats were treated for 3 weeks with imipramine (20 mg/kg) and tested for motor activity 24 h, 12, 33 and 40 days after treatment withdrawal. Ambulatory activity and rearing counts were recorded after challenge with the dopamine D2-like receptor agonist quinpirole (0.15 mg/kg). Imipramine increased the motor response to quinpirole, 24 h after treatment discontinuation. No relevant differences between the groups were found after 12 and 33 days. After 40 days, a decreased level of rearing was observed in the group treated with imipramine. These results show a reversal of the imipramine-induced dopaminergic supersensitivity after 40 days of chronic imipramine withdrawal and suggest that the mood-switches observed in bipolar patients following antidepressant treatment and subsequent withdrawal, i.e. mania followed by rebound depression, might depend upon parallel changes in the mesolimbic dopamine system sensitivity. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/12498916/Reversal_of_antidepressant_induced_dopaminergic_behavioural_supersensitivity_after_long_term_chronic_imipramine_withdrawal_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299902027310 DB - PRIME DP - Unbound Medicine ER -