GABA receptor agonism in the sublenticular central extended amygdala impairs medial forebrain bundle self-stimulation but GABA blockade does not enhance it

Abstract

The sublenticular central extended amygdala (SLEAc), which is important in medial forebrain bundle (MFB) self-stimulation, is heavily populated with GABAergic medium spiny neurons that intercommunicate via local axon collaterals. This study examines the role of GABAergic communication in the SLEAc in MFB self-stimulation. Male Long–Evans rats were given unilateral MFB stimulation electrodes and bilateral injection guide cannulae aimed at the SLEAc. Changes in the stimulation's reward efficacy and in the animals’ ability to respond for stimulation following 0.5 μl injections of saline, 50 ng of muscimol (GABA-A agonist), 75 ng of baclofen (GABA-B agonist), 25 ng of bicuculline methiodide (GABA-A antagonist), and 500 ng of phaclofen (GABA-B antagonist) were assessed using the rate–frequency curve shift paradigm. Injecting the receptor agonists ipsi- and contralateral to the stimulation site substantially decreased stimulation reward efficacy and responding. Baclofen's effects were more anatomically specific to the SLEAc and baclofen was less challenging to response rate than was muscimol. Ipsi- and contralateral injections of the receptor blockers and saline had no effect on either stimulation reward efficacy or response rate, although the blockers, especially phaclofen, sometimes enhanced response rate when injected into the globus pallidus or ventral pallidum. Comparing these results to others’ observations about GABAergic communication in the basal forebrain suggests that muscimol may have inhibited endemic SLEAc neurons while baclofen may have impaired the release of glutamate into the SLEAc from cortical and amygdalar afferents. These results also suggest functional differences between the two basal forebrain macrostructures of striatopallidum and extended amygdala.