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. 2023 Aug 1;34(5):243-250.
doi: 10.1097/FBP.0000000000000730. Epub 2023 Jun 30.

The role of lateral habenula NMDA receptors in tramadol-induced conditioning

Arman Hajikarim-Hamedani  1 , Amirhossein Heidari  1 , Mitra-Sadat Sadat-Shirazi  2 , Sarah Mahboubi  2 , Samira Raminfard  3 , Solmaz Khalifeh  4 , Mohammad-Reza Zarrindast  2   4   5
Affiliations

The role of lateral habenula NMDA receptors in tramadol-induced conditioning

Arman Hajikarim-Hamedani et al. Behav Pharmacol. .

Abstract

The role of the lateral habenula (LHb) as a hub for receiving and relaying signals from the limbic system to serotonergic, dopaminergic, and norepinephrinergic regions in the brainstem makes this area a critical region in the control of reward and addiction. Behavioral evidence reveals the vital role of the LHb in negative symptoms during withdrawal. In this investigation, we study the role of the LHb N-Methyl D-Aspartate receptor (NMDAR) in the modulation of tramadol reward. Male adult Wistar rats were used in this study. The effect of intra-LHb micro-injection of NMDAR agonist (NMDA, 0.1, 0.5, 2 µg/rat) and antagonist (D-AP5, 0.1, 0.5, 1 µg/rat) was evaluated in conditioned place preference (CPP) paradigm. The obtained results showed that intra-LHb administration of NMDA induced place aversion dose-dependently, while blockade of NMDAR in the LHb using D-AP5 micro-injection led to an increased preference score in the CPP task. Co-administration of NMDA (0.5 µg/rat) with tramadol (4 mg/kg) reduced preference score, while co-administration of D-AP5 (0.5 µg/rat) with a non-effective dose of tramadol (1 mg/kg) potentiate the rewarding effect of tramadol. LHb receives inputs from the limbic system and projects to the monoaminergic nuclei in the brainstem. It has been declared that NMDAR is expressed in LHb, and as obtained data revealed, these receptors could modulate the rewarding effect of tramadol. Therefore, NMDA receptors in the LHb might be a new target for modulating tramadol abuse.

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References

    1. Bassiony MM, Salah El-Deen GM, Yousef U, Raya Y, Abdel-Ghani MM, El-Gohari H, et al. (2015). Adolescent tramadol use and abuse in Egypt. Am J Drug Alcohol Abuse 41:206–211.
    1. Berridge KC, Robinson TE (2016). Liking, wanting, and the incentive-sensitization theory of addiction. Am Psychol 71:670–679.
    1. Bianco IH, Wilson SW (2009). The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philos Trans R Soc Lond B Biol Sci 364:1005–1020.
    1. Bromberg-Martin ES, Matsumoto M, Hikosaka O (2010). Distinct tonic and phasic anticipatory activity in lateral habenula and dopamine neurons. Neuron 67:144–155.
    1. Brown PL, Shepard PD (2016). Functional evidence for a direct excitatory projection from the lateral habenula to the ventral tegmental area in the rat. J Neurophysiol 116:1161–1174.

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