OCD

links: reference: 5-14-2021

OCD #

Acetylcholine/Glutamate #

• Elevated growth hormone responses to pyridostigmine in obsessive- compulsive disorder: evidence of cholinergic supersensitivity

  • (Pyridostigmine inhibits synaptic cleft acetylcholinesterase)
  • Treated by NMDA antagonists/correlated with higher levels of glutamate. R
  • The data suggest that cholinergic supersensitivity is present in obsessive-compulsive disorder

• Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

  • α4β2 nAChR is the most abundant nAChR subtype in brain areas implicated in OCD. Positive allosteric modulation significantly suppressed compulsive marble-burying behavior. No effect on anxiety-like behavior or locomotor activity.
  • Nicotine augmentation for refractory obsessive-compulsive disorder. A case report
    • These studies suggest that Nicotine acts both by facilitating Glutamatergic transmission and stabilizing the glutamatergic hyperactivity of the loop running from the orbitofrontal cortex to the cyngulate gyrus, the striatum and the thalamus.
      • Dafuq does stabilize really mean? Does it basically imply there’s a shortage of ACh and that the addition of it balances out all the necessary Gi and Gq nACh subtypes? Differences in the subunit composition of presynaptic nAChRs may contribute to distinct profiles of synaptic facilitation elicited by nicotine (Girod et al., 2000; Vogt and Regehr, 2001).
      • *It has been demonstrated that nicotine enhances glutamatergic transmission through nAChRs desensitisation and transiently enhances GABAergic transmission, leading to a reduction of inhibitory inputs due to nAChR (Mansvelder et al., 2002). *
      • Evidence for a complex influence of nicotinic acetylcholine receptors on hippocampal serotonin release
        • Nicotine causes an increase in Serotonin release (in the Hippocampus, which posesses both nAChR and M1) via binding to nicotinic heteroreceptors on 5-HT terminals, leading to an ACh discharge with inhibitory action on it.
        • A possible mechanism of the effect of nicotine on compulsions might be a reduction of acetylcholine release in the Striatum, and a decrease of Orbitofrontal Cortex hyperglutamatergia - orbitofrontal cortex activation has been found in Nicotine craving.
        • There are deficits in non-verbal memory and memory for actions in OCD patients. It is well known that antiglutamatergic agents have negative effects on memory, while cholinergic transmission may represent the fundamental system.