Acute and chronic effects by nicotine on striatal neurotransmission and synaptic plasticity in the female rat brain

Erika Lucente; Bo Söderpalm; Mia Ericson; Louise Adermark

doi:10.3389/fnmol.2022.1104648

Acute and chronic effects by nicotine on striatal neurotransmission and synaptic plasticity in the female rat brain

Front Mol Neurosci. 2023 Jan 12:15:1104648. doi: 10.3389/fnmol.2022.1104648. eCollection 2022.

Authors

Erika Lucente¹, Bo Söderpalm², Mia Ericson², Louise Adermark¹

Affiliations

¹ Integrative Neuroscience Unit, Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Abstract

Introduction: Tobacco use is in part a gendered activity, yet neurobiological studies outlining the effect by nicotine on the female brain are scarce. The aim of this study was to outline acute and sub-chronic effects by nicotine on the female rat brain, with special emphasis on neurotransmission and synaptic plasticity in the dorsolateral striatum (DLS), a key brain region with respect to the formation of habits.

Methods: In vivo microdialysis and ex vivo electrophysiology were performed in nicotine naïve female Wistar rats, and following sub-chronic nicotine exposure (0.36 mg/kg free base, 15 injections). Locomotor behavior was assessed at the first and last drug-exposure.

Results: Acute exposure to nicotine ex vivo depresses excitatory neurotransmission by reducing the probability of transmitter release. Bath applied nicotine furthermore facilitated long-term synaptic depression induced by high frequency stimulation (HFS-LTD). The cannabinoid 1 receptor (CB1R) agonist WIN55,212-2 produced a robust synaptic depression of evoked potentials, and HFS-LTD was blocked by the CB1R antagonist AM251, suggesting that HFS-LTD in the female rat DLS is endocannabinoid mediated. Sub-chronic exposure to nicotine in vivo produced behavioral sensitization and electrophysiological recordings performed after 2-8 days abstinence revealed a sustained depression of evoked population spike amplitudes in the DLS, with no concomitant change in paired pulse ratio. Rats receiving sub-chronic nicotine exposure further demonstrated an increased neurophysiological responsiveness to nicotine with respect to both dopaminergic- and glutamatergic signaling. However, a tolerance towards the plasticity facilitating property of bath applied nicotine was developed during sub-chronic nicotine exposure in vivo. In addition, the dopamine D2 receptor agonist quinpirole selectively facilitate HFS-LTD in slices from nicotine naïve rats, suggesting that the tolerance may be associated with changes in dopaminergic signaling.

Conclusion: Nicotine produces acute and sustained effects on striatal neurotransmission and synaptic plasticity in the female rat brain, which may contribute to the establishment of persistent nicotine taking habits.

Keywords: LTD; dopamine; electrophysiology; endocannabinoid; female; nicotine; striatum.