Excessive drinking and checking in the rat model of Schedule-Induced Polydipsia reveal impaired bi-directional plasticity at BNST GABA synapses
Compulsions, defined by debilitating repetitive actions, permeate many mental illnesses and are challenging to treat partly because of a limited understanding of their neurobiological underpinnings. Accumulating evidence suggests the rodent model of Schedule-Induced Polydipsia (SIP) as a promising pre-clinical assay to elucidate the neurobiological and behavioural manifestations of compulsivity. In the rodent SIP paradigm, susceptible rats develop adjunctive excessive drinking when they are chronically food restricted and presented with food pellets according to a fixed-time schedule. We found that normally, bi-directional plasticity of GABA synapses in the oval bed nucleus of the stria terminalis (ovBNST) tightly followed the rats satiety state where low-frequency stimulation-induced potentiation (LTPO_SCPCAPGABAC_SCPCAP) prevailed in sated rats whilst food restriction uncovered long-term depression (LTDO_SCPCAPGABAC_SCPCAP). In rats that developed excessive drinking during SIP, removing the caloric restriction failed at reverting LTDO_SCPCAPGABAC_SCPCAP to LTPO_SCPCAPGABAC_SCPCAP whereas bi-directional plasticity at ovBNST GABA synapses was unaltered in low-drinking SIP-trained rats. Excessive drinking ceased in polydipsic rats removed from their caloric restriction; however, these rats retained a form of compulsive schedule-induced checking (SIC) and impaired plasticity at ovBNST GABA synapses for several days following termination of the caloric restriction. We conclude that altered bi-directional plasticity at ovBNST GABA synapses is a neurophysiological trace of compulsivity in susceptible rats in the SIP model.