The interaction between dopaminergic and cholinergic pathways in the induction of behavioral responses has been previously established. In the brain, M2 receptors are found predominantly in presynaptic cholinergic neurons as autoreceptors, and in dopaminergic neurons as heteroceptors, suggesting a control role of acetylcholine and dopamine release, respectively. Our aim was to investigate the role of M2 receptors on the yawning and genital grooming of rats induced by apomorphine, a dopaminergic receptor agonist, focusing on the interaction between cholinergic and dopaminergic pathways. Initially, the effect of atropine, a non-selective muscarinic antagonist, on yawning and genital grooming induced by apomorphine (100μg/kg s.c.) was analyzed. Atropine doses of 0.5, 1 and 2mg/kg i.p. were administered to Wistar rats 30min before induction of the behavioral responses by apomorphine. Number of yawns and time spent genital grooming were quantified over a 60min period. Apomorphine-induced yawning was increased by low dose (0.5mg/kg i.p.) but not by high doses (1 and 2mg/kg, i.p.) of atropine. Genital grooming was antagonized by 2mg/kg i.p. of atropine and showed no changes at the other doses tested. Tripitramine, a selective M2 cholinergic antagonist, was used as a tool for distinguishing between M2 and all other muscarinic receptor subtypes in yawning and genital grooming. Tripitramine doses of 0.01, 0.02 and 0.04μmol/kg i.p. were administered to Wistar rats 30min before apomorphine (100μg/kg s.c.). Number of yawns and time spent genital grooming were also quantified over a 60min period. Tripitramine 0.01μmol/kg increased all parameters. Higher doses, which possibly block all subtypes of muscarinic receptor, did not modify the response of apomorphine, suggesting a non-selective effect of tripitramine at these doses. Given that low doses of tripitramine increased the behavioral responses induced by apomorphine and that the main distribution of the M2 receptor is presynaptic, we raised the hypothesis that tripitramine may alter cholinergic and/or dopaminergic transmission in brain areas responsible for induction of yawning and genital grooming in rats, possibly by control of acetylcholine and/or dopamine release. In addition, the present study showed the involvement of M2 cholinergic receptors in the complex mechanisms of functional interactions between dopaminergic and cholinergic systems involved in the control of yawning and genital grooming.
Gamberini MT, Bolognesi ML, Nasello AG (2012). The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming. NEUROSCIENCE LETTERS, 531, 91-95 [10.1016/j.neulet.2012.09.052].
The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming
BOLOGNESI, MARIA LAURA;
2012
Abstract
The interaction between dopaminergic and cholinergic pathways in the induction of behavioral responses has been previously established. In the brain, M2 receptors are found predominantly in presynaptic cholinergic neurons as autoreceptors, and in dopaminergic neurons as heteroceptors, suggesting a control role of acetylcholine and dopamine release, respectively. Our aim was to investigate the role of M2 receptors on the yawning and genital grooming of rats induced by apomorphine, a dopaminergic receptor agonist, focusing on the interaction between cholinergic and dopaminergic pathways. Initially, the effect of atropine, a non-selective muscarinic antagonist, on yawning and genital grooming induced by apomorphine (100μg/kg s.c.) was analyzed. Atropine doses of 0.5, 1 and 2mg/kg i.p. were administered to Wistar rats 30min before induction of the behavioral responses by apomorphine. Number of yawns and time spent genital grooming were quantified over a 60min period. Apomorphine-induced yawning was increased by low dose (0.5mg/kg i.p.) but not by high doses (1 and 2mg/kg, i.p.) of atropine. Genital grooming was antagonized by 2mg/kg i.p. of atropine and showed no changes at the other doses tested. Tripitramine, a selective M2 cholinergic antagonist, was used as a tool for distinguishing between M2 and all other muscarinic receptor subtypes in yawning and genital grooming. Tripitramine doses of 0.01, 0.02 and 0.04μmol/kg i.p. were administered to Wistar rats 30min before apomorphine (100μg/kg s.c.). Number of yawns and time spent genital grooming were also quantified over a 60min period. Tripitramine 0.01μmol/kg increased all parameters. Higher doses, which possibly block all subtypes of muscarinic receptor, did not modify the response of apomorphine, suggesting a non-selective effect of tripitramine at these doses. Given that low doses of tripitramine increased the behavioral responses induced by apomorphine and that the main distribution of the M2 receptor is presynaptic, we raised the hypothesis that tripitramine may alter cholinergic and/or dopaminergic transmission in brain areas responsible for induction of yawning and genital grooming in rats, possibly by control of acetylcholine and/or dopamine release. In addition, the present study showed the involvement of M2 cholinergic receptors in the complex mechanisms of functional interactions between dopaminergic and cholinergic systems involved in the control of yawning and genital grooming.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
