Effects of GABA Receptor Blockade on Lateral Habenula Glutamatergic Neuron Activity Following Morphine Injection in the Rat: an Electrophysiological Study

Overview

Journal Res Pharm Sci

Specialty Chemistry

Date 2023 Feb 27

PMID 36846735

Authors

Elahe Amohashemi

Hojjatallah Alaei

Parham Reisi

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: The lateral habenula (LHb), a key area in the regulation of the reward system, exerts a major influence on midbrain neurons. It has been shown that the gamma-aminobutyric acid (GABA)- ergic system plays the main role in morphine dependency. The role of GABA type B receptors (GABAR) in the regulation of LHb neural activity in response to morphine, remains unknown. In this study, the effect of GABAR blockade in response to morphine was assessed on the neuronal activity in the LHb.

Experimental Approach: The baseline firing rate was recorded for 15 min, then morphine (5 mg/kg; s.c) and phaclofen (0, 0.5, 1, and 2 μg/rat), a GABAR' antagonist, were microinjected into the LHb. Their effects on firing LHb neurons were investigated using an extracellular single-unit recording in male rats.

Findings/results: The results revealed that morphine decreased neuronal activity, and GABAR blockade alone did not have any effect on the neuronal activity of the LHb. A low dose of the antagonist had no significant effect on neuronal firing rate, while blockade with doses of 1 and 2 μg/rat of the antagonist could significantly prevent the inhibitory effects of morphine on the LHb neuronal activity.

Conclusion And Implications: This result indicated that GABAR have a potential modulator effect, in response to morphine in the LHb.

Citing Articles

The reinstatement of the expression phase of morphine-induced conditioned place preference in male Wistar rats under ventral tegmental area stimulation and brief inactivation.

Pour M, Alaei H Res Pharm Sci. 2024; 18(6):676-695.

PMID: 39005563 PMC: 11246116. DOI: 10.4103/1735-5362.389957.

References

Sotty F, Danik M, Manseau F, Laplante F, Quirion R, Williams S . Distinct electrophysiological properties of glutamatergic, cholinergic and GABAergic rat septohippocampal neurons: novel implications for hippocampal rhythmicity. J Physiol. 2003; 551(Pt 3):927-43. PMC: 2343277. DOI: 10.1113/jphysiol.2003.046847. View

Chebib M, Hinton T, Schmid K, Brinkworth D, Qian H, Matos S . Novel, potent, and selective GABAC antagonists inhibit myopia development and facilitate learning and memory. J Pharmacol Exp Ther. 2008; 328(2):448-57. PMC: 2630368. DOI: 10.1124/jpet.108.146464. View

Meye F, Lecca S, Valentinova K, Mameli M . Synaptic and cellular profile of neurons in the lateral habenula. Front Hum Neurosci. 2014; 7:860. PMC: 3863943. DOI: 10.3389/fnhum.2013.00860. View

Paxinos G, Watson C, Emson P . AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. J Neurosci Methods. 1980; 3(2):129-49. DOI: 10.1016/0165-0270(80)90021-7. View

Flanigan M, Aleyasin H, Takahashi A, Golden S, Russo S . An emerging role for the lateral habenula in aggressive behavior. Pharmacol Biochem Behav. 2017; 162:79-86. PMC: 5659946. DOI: 10.1016/j.pbb.2017.05.003. View

Ghamkharinejad G, Marashi S, Foolad F, Javan M, Fathollahi Y . Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits. PLoS One. 2021; 16(9):e0253902. PMC: 8428970. DOI: 10.1371/journal.pone.0253902. View

Hutt A . The population firing rate in the presence of GABAergic tonic inhibition in single neurons and application to general anaesthesia. Cogn Neurodyn. 2013; 6(3):227-37. PMC: 3368058. DOI: 10.1007/s11571-011-9182-9. View

Ueda H, Ueda M . Mechanisms underlying morphine analgesic tolerance and dependence. Front Biosci (Landmark Ed). 2009; 14(14):5260-72. DOI: 10.2741/3596. View

Golden S, Heshmati M, Flanigan M, Christoffel D, Guise K, Pfau M . Basal forebrain projections to the lateral habenula modulate aggression reward. Nature. 2016; 534(7609):688-92. PMC: 4930107. DOI: 10.1038/nature18601. View

10.

Zhang L, Hernandez V, Swinny J, Verma A, Giesecke T, Emery A . A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling. Transl Psychiatry. 2018; 8(1):50. PMC: 5865187. DOI: 10.1038/s41398-018-0099-5. View

11.

Kim J, Ham S, Hong H, Moon C, Im H . Brain Reward Circuits in Morphine Addiction. Mol Cells. 2016; 39(9):645-53. PMC: 5050528. DOI: 10.14348/molcells.2016.0137. View

12.

Stamatakis A, Stuber G . Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance. Nat Neurosci. 2012; 15(8):1105-7. PMC: 3411914. DOI: 10.1038/nn.3145. View

13.

Tuominen L, Tuulari J, Karlsson H, Hirvonen J, Helin S, Salminen P . Aberrant mesolimbic dopamine-opiate interaction in obesity. Neuroimage. 2015; 122:80-6. DOI: 10.1016/j.neuroimage.2015.08.001. View

14.

Lecca S, Pelosi A, Tchenio A, Moutkine I, Lujan R, Herve D . Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice. Nat Med. 2016; 22(3):254-61. DOI: 10.1038/nm.4037. View

15.

Dougherty P, Qiao J, Wiggins R, Dafny N . Microiontophoresis of cocaine, desipramine, sulpiride, methysergide, and naloxone in habenula and parafasciculus. Exp Neurol. 1990; 108(3):241-6. DOI: 10.1016/0014-4886(90)90129-g. View

16.

Luscher C, Jan L, Stoffel M, Malenka R, Nicoll R . G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron. 1997; 19(3):687-95. DOI: 10.1016/s0896-6273(00)80381-5. View

17.

Weiss T, Veh R . Morphological and electrophysiological characteristics of neurons within identified subnuclei of the lateral habenula in rat brain slices. Neuroscience. 2010; 172:74-93. DOI: 10.1016/j.neuroscience.2010.10.047. View

18.

Bianco I, Wilson S . The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philos Trans R Soc Lond B Biol Sci. 2008; 364(1519):1005-20. PMC: 2666075. DOI: 10.1098/rstb.2008.0213. View

19.

Fartootzadeh R, Alaei H, Reisi P . Mutual assistance of nucleus accumbens cannabinoid receptor-1 and orexin receptor-2 in response to nicotine: a single-unit study. Res Pharm Sci. 2021; 16(2):173-181. PMC: 8102922. DOI: 10.4103/1735-5362.310524. View

20.

Galaj E, Han X, Shen H, Jordan C, He Y, Humburg B . Dissecting the Role of GABA Neurons in the VTA SNr in Opioid Reward. J Neurosci. 2020; 40(46):8853-8869. PMC: 7659457. DOI: 10.1523/JNEUROSCI.0988-20.2020. View