Nicotinic mechanisms of memory: effects of acute local DHβE and MLA infusions in the basolateral amygdala

Abstract

Nicotine has been shown to improve working memory. The neural mechanisms underlying this effect are still being determined. The ventral hippocampus is critical for nicotinic effects on memory. Local ventral hippocampal infusions of either the nicotinic α7 nicotinic receptor antagonist methyllycaconitine (MLA) or the α4β2 nicotinic receptor antagonist dihydro-β-erythroidine (DHβE) caused working memory impairments, but no additive effects were seen. Other areas, such as the amygdala, also likely play important roles in nicotinic effects on memory. Amygdalar lesions cause memory impairment and there is a dense concentration of nicotinic receptors in the basolateral amygdala. The current study used local basolateral amygdalar infusions of the nicotinic antagonists MLA and DHβE to determine the involvement of α7 and α4β2 nicotinic receptors in spatial working and reference memory. Rats ( n=8) were trained in the 16-arm radial maze and were implanted with bilateral infusion cannulae into the basolateral amygdala. Acute infusions of MLA (6.75 μg/side, P<0.0005) or DHβE (3.38 μg/side, P<0.025) caused significant working memory impairments. When given together MLA and DHβE did not produce an additive effect. In fact, the 6.75 μg/kg dose of DHβE produced a significant ( P<0.0005) attenuation of the MLA-induced working memory impairment. Significant effects were not seen with reference memory or response latency. Nicotinic systems in the basolateral amygdala, as in the ventral hippocampus, are important for spatial working memory. In both the basolateral amygdala and the ventral hippocampus, MLA and DHβE individually caused working memory impairments. The lowest effective dose of DHβE was lower in the basolateral amygdala than in the ventral hippocampus. In both the basolateral amygdala and the ventral hippocampus, combined MLA and DHβE treatment did not produce additive working memory deficits. Unlike in the ventral hippocampus, the addition of DHβE to MLA in the basolateral amygdala significantly reduced the MLA-induced working memory deficit.