The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not β2- or α7-nicotinic acetylcholine receptor subunit knockout mice

  title={The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not $\beta$2- or $\alpha$7-nicotinic acetylcholine receptor subunit knockout mice},
  author={Rebecca L. Rabenstein and Barbara J. Caldarone and Marina R. Picciotto},
RationaleIncreases in cholinergic transmission are linked to depression in human subjects and animal models. We therefore examined the effect of decreasing nicotinic acetylcholine receptor (nAChR) activity in tests of antidepressant efficacy using C57BL/6J mice.ObjectivesWe determined whether the noncompetitive nAChR antagonist mecamylamine had antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST). These experiments were repeated in mice lacking either the β2… 

Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests

A strategy involving antagonism of central α4β2 and/or α7 nAChRs induced antidepressant-like effects in mice, and could potentially lead to the development of novel antidepressant therapeutics.

Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380

Results demonstrate that activation of a small population of β2* nAChRs (10–40%) is sufficient to elicit sazetidine’s antidepressant-like actions without producing tolerance and suggest that ligands that activate β2- nA ChRs would be promising targets for the development of a new class of antidepressant.

Antidepressant-like effects of nicotine and mecamylamine in the mouse forced swim and tail suspension tests: role of strain, test and sex

It is hypothesize that nicotine and mecamylamine produce antidepressant-like effects through partially different mechanisms through partly different mechanisms.

Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test

The data suggest that the activity of citalopram and reboxetine in the mouse forced swim test can be enhanced by agonists at either α4β2 or α7 nicotinic acetylcholine receptor receptors, suggesting that both nicotinIC acetyl choline receptor subtypes may be involved in the nicotine-enhanced action of antidepressants.

Antidepressant-like effects of lobeline in mice: Behavioral, neurochemical, and neuroendocrine evidence

Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice

Guanfacine has a robust antidepressant-like effect and can reverse a depression-like state induced by increased acetylcholine (ACh) signaling, and data suggest that different brain areas are recruited in female and male mice, despite similar behavioral responses to guanfacine.

Behavioral effects of nicotinic antagonist mecamylamine in a rat model of depression: prefrontal cortex level of BDNF protein and monoaminergic neurotransmitters

The present data suggest that MEC possesses antidepressant and anxiolytic-like activities in rats exposed to CRS, which may be in part mediated by reducing HPA axis hyperactivity and increasing PFC level of BDNF and monoamines.



Antidepressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression

Results not only suggest a role for nAChRs in the development of a depressive-like syndrome, but also that subtype-selective nA ChR agonists, such as SIB-1508Y, may offer a novel therapeutic approach to the treatment of depression.

Mice Deficient in the α7 Neuronal Nicotinic Acetylcholine Receptor Lack α-Bungarotoxin Binding Sites and Hippocampal Fast Nicotinic Currents

It is demonstrated that the α7 subunit is not essential for normal development or for apparently normal neurological function, but the mice may prove to have subtle phenotypic abnormalities and will be valuable in defining the functional role of this gene product in vivo.

Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain

It is reported here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the β2-subunit mutation, and electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application.

Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents.

It is demonstrated that the alpha7 subunit is not essential for normal development or for apparently normal neurological function, but the mice may prove to have subtle phenotypic abnormalities and will be valuable in defining the functional role of this gene product in vivo.

Conditional Expression in Corticothalamic Efferents Reveals a Developmental Role for Nicotinic Acetylcholine Receptors in Modulation of Passive Avoidance Behavior

It is suggested that high-affinity nAChRs expressed on corticothalamic neurons during development are critical for baseline PA performance and provide a potential neuroanatomical substrate for changes induced by prenatal nicotine exposure leading to long-term behavioral and cognitive deficits.

Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice

Oral AMI administration provides a valid model for behavioral assessment of antidepressant-like effects in knockout and transgenic mice maintained on a B6 background, but the effectiveness of oral AMI varies depending on sex, duration of treatment, and the depression model used.

Antidepressant effects of nicotine in an animal model of depression

Data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the FSL rats, and suggest that Nicotinic agonists may have therapeutic benefits in depressive disorders.

Nicotinic receptors in the brain

  • C. Vidal
  • Biology, Psychology
    Molecular and chemical neuropathology
  • 1996
The recent studies using electrophysiological biochemical and behavioral approaches suggest that the prefrontal cortex is a major target site for the cognitive actions of nicotine.

Nicotinic acetylcholine receptors as targets for antidepressants

Preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder.

Nicotinic Receptors in the Brain: Links between Molecular Biology and Behavior