Locomotor activation and dopamine release produced by nicotine and isoarecolone in rats

Abstract

3 Isoarecolone (1-200 pM) evoked predominantly mecamylamine-sensitive dopamine release from both striatal and cortical synaptosomes, with a potency at least 20 times less than that of nicotine. The maximum effect of isoarecolone was less than that of nicotine, particularly in the frontal cortex preparation. 4 In control rats treated chronically with saline, neither nicotine nor isoarecolone had clear effects on locomotor activity at the doses tested. Chronic treatment with nicotine clearly sensitized rats to the locomotor activating effect of nicotine; there was only weak cross-sensitization to isoarecolone. The maximum effect of isoarecolone was seen at a dose about 40 times larger than that of nicotine. 5The low potency and efficacy of isoarecolone in facilitating sensitized locomotor activity resembled its lower potency and efficacy, compared with nicotine, in evoking dopamine release in vitro. The agonist proffle of the nicotinic receptor population mediating dopamine release may determine the pharmacological characteristics of consequent locomotor behaviour.

Methamphetamine-Like Discriminative-Stimulus Effects of Nicotinic Agonists

“…Based upon other behavioral and biochemical findings, however, isoarecolone has been forwarded as a nicotinic partial agonist (Reavill et al, 1987;Whiteaker et al, 1995;Mirza et al, 1996;Hahn et al, 2003;Shoaib, 2006). The present findings that the highest doses of isoarecolone produced only an intermediate level of substitution for MA might be considered supporting evidence for that view.…”

Dose‐related neuroprotective effects of chronic nicotine in 6‐hydroxydopamine treated rats, and loss of neuroprotection in α4 nicotinic receptor subunit knockout mice

“…Doses of 0.75, 1.5 and 3.0 mg kg 71 day 71 are likely to achieve brain nicotine concentrations of 0.2 to at least 0.5 mM (Rowell & Li, 1997). This range approximates the EC 50 reported for nicotine-evoked dopamine release in striatal synaptosomes and slices (0.16 ± 0.5 mM) (Grady et al, 1992;Whiteaker et al, 1995;Clarke & Reuben, 1996;Wonnacott, 1997), and falls within the range that is maximally protective against neurotoxic damage in vitro (approximately 0.1 ± 5 mM) (Donnelly-Roberts et al, 1996;Semba et al, 1996). The dose of 3.0 mg kg 71 day 71 was of particular interest, as it is widely cited as a dose that re¯ects plasma nicotine concentrations in smokers, where smokers demonstrate a diminished incidence of PD (Baron, 1986;Morens et al, 1995).…”

Increased Sensitivity to Nicotine-Induced Seizures in Mice Expressing the L250T α7 Nicotinic Acetylcholine Receptor Mutation

“…This finding may suggest a role for ␣7 nAChRs in locomotor activity. Increasing evidence indicates that nicotine stimulates locomotor activity in animals by acting on nAChRs found along the mesostriatal dopaminergic pathway (Whiteaker et al, 1995;Louis and Clarke, 1998;Wonnacott et al, 2000). Although studies have demonstrated the involvement of ␣6 nAChR subunits in nicotineelicited locomotion , the role of ␣7 nAChRs seems to be negligible (Grottick et al, 2000;Kempsill and Pratt, 2000).…”

“…In humans, at doses obtained from cigarette smoking, nicotine can improve cognitive function, increase attention, and reduce fatigue and anxiety (Kassel and Shiffman, 1997;Newhouse et al, 1997;Levin and Rezvani, 2000). In laboratory animals, low doses of nicotine affect nociception (Jurna et al, 1993;Damaj et al, 1998;Marubio et al, 1999), cardiovascular responses (Neff et al, 1998;Marano et al, 1999), locomotor activity (Whiteaker et al, 1995;, thermoregulation (Lupien and Bray, 1988), and learning, memory, and attention (Levin et al, 1994;Stolerman et al, 2000). High doses of nicotine induce clonic-tonic seizures (Miner et al, 1984;Damaj et al, 1999).…”