Effects of chronic ethanol consumption on rat GABAA and strychnine-sensitive glycine receptors expressed by lateral/basolateral amygdala neurons

Abstract

It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABA(A) and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABA(A) receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor's response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABA(A) receptors composed of unique alpha subunits were differentially sensitive to acute ethanol. Likewise, the presence of the beta subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the alpha(2) subunit. Our results suggest that the facilitation of GABA(A) receptors during chronic ethanol exposure may help explain the maintenance of ethanol's anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABA(A) and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure.

Mechanisms of Reversible GABAAReceptor Plasticity after Ethanol Intoxication

“…EtOH-induced changes within mesolimbic circuits include region-specific changes in GABA A R ␣1 and ␣4 subunit peptide expression and receptor function in the amygdala, nucleus accumbens, ventral tegmental area (Papadeas et al, 2001;McCool et al, 2003), the hippocampal CA1 and dentate gyrus (present study) (Matthews et al, 1998), and cortex (Mhatre et al, 1993;Matthews et al, 1998). Interestingly, a single EtOH dose was also demonstrated to produce increases in GABAergic synaptic transmission via presynaptic mechanisms in the ventral tegmental area, with recovery observed by 2 weeks after EtOH withdrawal (Melis et al, 2002).…”

Chronic Ethanol Ingestion FacilitatesN-Methyl-d-aspartate Receptor Function and Expression in Rat Lateral/Basolateral Amygdala Neurons

“…To prepare brain slices, rats were anesthetized with isoflurane and decapitated. Tissue slices containing the BLA were prepared as reported previously (McCool et al, 2003). After preparation, slices were stored in oxygenated Ringer's solution for up to 5 h. Individual neurons were isolated from tissue by incubation of a single slice for 20 min at 37°C in oxygenated Ringer's solution containing 0.5 to 0.75 mg/ml Pronase protease (Calbiochem, San Diego, CA).…”

Strychnine and taurine modulation of amygdala-associated anxiety-like behavior is ‘state’ dependent

“…Sessions were performed using the elevated plusmaze [37] To measure anxiety with the light/dark box [31], individuals were placed in the 'light' side of a 40cm × 40cm plexiglass arena divided equally into 'light' and 'dark' sides by an opaque plexiglass insert (Rat Truscan Activity Arena, Coulbourn Instruments, Allentown PA) illuminated by ambient room lighting to ~400lux at the center of the 'light' side. The geometric center of the animal ±1.3cm was followed for five minutes by two infrared senor rings surrounding the entire apparatus, one in the floor plane and one located ~15cm above the floor to measure rearing behavior.…”