Motivated behaviour - the role of GABA receptor subtypes in the nucleus accumbens

The role of ?-aminobutyric acid (GABA) in modulating nucleus accumbens (Acb) function was investigated using feeding in rats as a model of motivation. Feeding encompasses processes associated with ‘appetite’, ‘satiety’ and ‘reward’. Distinct neurotransmitter systems in the Acb have been demonstrated to control specific behavioural mechanisms subserving these motivational processes. The Acb has been described as an interface between ‘motivation’ and ‘action’. It is involved in the modulation of feeding, sexual behaviour, defensive behaviours and drug seeking. Over 97% of Acb neurons are GABAergic and GABA mimetics robustly increase food intake in satiated animals. One current hypothesis suggests that GABAA and GABAB receptors gate control of ingestive motor responses via the same circuit but this circuit cannot control more complex goal-directed behaviours (Kelley et al., 2005). Temporal changes in the feeding related ‘behavioural satiety sequence’ (BSS) correlate with mechanisms that override satiety. The BSS is sensitive to effects on consummatory behaviour. Satiated rats given chow following intra-Acb infusions of a GABAB receptor agonist fed voraciously and the BSS was delayed but all other behaviours were still present. The pattern was similar with fasting and a systemically administered benzodiazepine but, with a µ-opioid agonist (postulated to increase the incentive value of food), the peak in feeding was delayed. A GABAA receptor agonist induced feeding but all other behaviours were significantly reduced at all effective doses. In a second order operant schedule that independently measured appetitive and consummatory behaviour, the GABAA and opioid receptor agonists had no effect on responding but the GABAB receptor agonist increased reinforced responding in a dose dependent manner. Several other behavioural indices of motivation also increased, suggesting behaviourally selective effects. These results are inconsistent with the hypothesis described above. Intra-Acb GABA receptor subtype stimulation led to significant differences in the location and magnitude of activity in motivation related brain structures, particularly the lateral hypothalamus and amygdala, which were revealed using Fos-like immunoreactivity as a marker. The differential modulation of feeding behaviour via GABA receptor subtypes in the Acb is used to construct a modified model to explain endogenous inhibitory motivational control.