Nicotine Rather Than Non-Nicotine Substances in 3R4F WCSC Increases Behavioral Sensitization and Drug-Taking Behavior in Rats

Abstract

Introduction Nicotine increases reinforcing effects of cigarette smoking by upregulating glutamate and dopamine releases via stimulation of nicotinic acetylcholine receptors (nAChRs) in the dorsal striatum (CPu). The present study was conducted to evaluate whether non-nicotine substances in cigarette smoke potentiate nicotine-induced behaviors by increasing glutamate and dopamine concentrations in the CPu. Methods Changes in the levels of glutamate and dopamine in the CPu were analyzed using a glutamate colorimetric assay and dopamine enzyme-linked immunosorbent assay, respectively, after repeated administration of nicotine or whole cigarette smoke condensate (WCSC) in male Sprague-Dawley rats. Changes in locomotion and drug-taking behavior were analyzed using the measurements of locomotor activity and self-administration under a fixed ratio 1 schedule in response to repeated administration of nicotine or WCSC. Results Repeated subcutaneous (s.c.) injections of nicotine (0.25 mg/kg/day) for seven consecutive days significantly increased the levels of glutamate and dopamine in the CPu. Similar results were obtained from repeated injections of WCSC (0.25 mg/kg nicotine/day, s.c.) extracted from 3R4F Kentucky reference cigarettes. Parallel with the increases in the neurotransmitter levels in the CPu, both nicotine and WCSC increased locomotor activity and self-administration (0.03 mg/kg nicotine/infusion). However, repeated injections of WCSC did not change the nicotine-induced increases in neurotransmitter levels, locomotor activity, and self-administration. Conclusions Nicotine rather than non-nicotine substances in WCSC play a major role in potentiating behavioral sensitization and drug-taking behavior via elevation of glutamate and dopamine concentrations in the CPu of rats. Implications WCSC does not augment the nicotine-induced increases in behavioral sensitization, drug-taking behavior, and glutamate and dopamine concentrations, suggesting that non-nicotine substances do not potentiate the nicotine-induced behaviors by increasing the concentrations of the neurotransmitters in the CPu. These findings imply that nicotine, but not non-nicotine substances in WCSC, may be a major contributor that induces tobacco dependence in rats.

Catharanthine Modulates Mesolimbic Dopamine Transmission and Nicotine Psychomotor Effects via Inhibition of α6-Nicotinic Receptors and Dopamine Transporters

“…Food training and surgery for catheter implantation were performed as described previously. , To facilitate the acquisition of operant chambers, rats were trained to press a lever for 45 mg of food pellets (BioServ, Frenchtown, NJ, USA) under a fixed ratio 1 (FR 1) schedule of reinforcement during 1 h sessions. After the acquisition criterion (over 80 food pellets/h for three consecutive days), rats were anesthetized with 2–4% isoflurane.…”

“…Nicotine SA test was performed as described previously. , After recovery from intravenous (iv) catheter surgery, rats began NIC (0.03 mg/kg/infusion) SA during a daily 1 h session for at least 14 consecutive days under the FR 1 schedule of reinforcement. During the SA sessions, a response on the active lever (drug-paired lever) resulted in a 0.1 mL iv delivery of nicotine for 4.1 s. Drug infusion was paired with the illumination of a cue light above the active lever; the house light was turned off during infusion of drugs.…”

Cofilin linked to GluN2B subunits of NMDA receptors is required for behavioral sensitization by changing the dendritic spines of neurons in the caudate and putamen after repeated nicotine exposure

“…Nicotine hydrogen tartrate salt was purchased from Sigma-Aldrich (St. Louis, MO, USA), dissolved in sterile 0.9% physiological saline (NaCl), and the pH was adjusted to 7.2−7.4 with sodium hydroxide (NaOH). Nicotine was administered subcutaneously (s.c.) in a 1 mL volume, and the nicotine concentration (0.3 mg/kg/day) was determined in previous studies [11]. The rats were randomly divided and were administered saline or nicotine for seven consecutive days.…”

“…Nicotine releases various neurotransmitters, including glutamate and dopamine, by binding to the nicotinic acetylcholine receptors (nAChRs) in the caudate and putamen (CPu), a region involved primarily in habit formation like tobacco smoking [7][8][9][10][11]. These increases in neurotransmissions lead to changes in the morphology of dendritic spines in the neurons of the CPu, developing habit learning [12][13][14].…”

Restoring Antioxidant Levels of Nicotine Injected Rats Using Suggested Dietary Formulas

“…Nicotine (0.25 mg/kg of rat body weight per day) was given subcutaneously into normal healthy male albino rats for 7 days using the method described by (Kim et al, 2022).…”