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J Neuroendocrinol. 2012 Apr;24(4):664-73. doi: 10.1111/j.1365-2826.2011.02239.x.

Tonic regulation of GABAergic synaptic activity on vasopressin neurones by cannabinoids.

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Department of Anatomy and Neurobiology and Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA.


Synaptic activity in magnocellular neurosecretory neurones is influenced by the retrograde (i.e. somatodendritic) release of vasopressin, oxytocin and cannabinoids (CBs). For oxytocin neurones, oxytocin exerts constitutive effects on pre-synaptic activity through its ability to release CBs post-synaptically. In the present study, we examined evoked inhibitory post-synaptic currents (eIPSCs) and spontaneous inhibitory post-synaptic currents (sIPSCs) in identified vasopressin (VP) neurones in coronal slices from virgin rats to determine: (i) the extent to which CBs may also tonically modulate VP synaptic activity; and (ii) to determine whether depolarisation-induced suppression of inhibition was present in VP neurones, and if so, whether it was mediated by VP or CBs. The CB1 antagonists AM251 (1 μm) and SR14171 (1 μm) consistently increased the frequency of sIPSCs in VP neurones without affecting their amplitude, suggesting a tonic CB presence. This effect on frequency was independent of action potential activity, and blocked by chelating intracellular calcium with 10 mm ethylene glycol tetraacetic acid (EGTA). AM251 also increased the amplitude of eIPSCs and decreased the paired-pulse ratio (PPR) in VP neurones-effects that were completely blocked with even low (1 mm EGTA) internal calcium chelation. Bouts of evoked firing of VP neurones consistently suppressed sIPSCs but had no effect on eIPSCs or the PPR. This depolarisation-induced suppression of IPSCs was reduced by AM251, and was totally blocked by 10 μm of the mixed vasopressin/oxytocin antagonist, Manning compound. We then tested the effect of vasopressin on IPSCs at the same time as blocking CB1 receptors. Vasopressin (10-100 nm) inhibited sIPSC frequency but had no effect on sIPSC or eIPSC amplitudes, or on the PPR, in the presence of AM251. Taken together, these results suggest a tonic, pre-synaptic inhibitory modulation of IPSCs in VP neurones by CBs that is largely dependent on post-synaptic calcium, and an inhibitory effect of VP on IPSCs that is independent of CB release.

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