Injections of Tacrine and Scopolamine into the Nucleus Accumbens: Opposing Effects of Immediate vs Delayed Posttrial Treatment on Memory of an Open Field

Abstract

Using the paradigm of habituation learning in the open field, we tested the effects of microinjections of the nonspecific acetylcholine-esterase inhibitor tacrine (0.1, 1.0, 10.0 μMg), and the muscarinic receptor antagonist scopolamine (0.1, 1.0, 10.0 μg) into the core of the nucleus accumbens. When injected immediately after the first exposure to the open field (posttrial), tacrine dose-dependently enhanced habituation of rearing behavior during the test on the following day, indicating a facilitation of memory. In contrast, scopolamine impaired habituation of rearing behavior at the two lower doses, but not at the highest dose. When scopolamine or tacrine (10.0 μMg) was injected with a delay of 5 h after the learning trial, both drugs impaired habituation of rearing on the following day. The effects on locomotor activity differed from those on rearing behavior. Here, habituation on Day 2 was observed only in those animals which had received posttrial injections of vehicle or 10 μMg of tacrine on the day before, whereas in animals which had received the two lower doses of tacrine, locomotor activity on Day 2 was not significantly decreased. In animals with posttrial treatment of scopolamine, locomotor activity on Day 2 was even enhanced, especially with the lower doses. No such effects were observed when scopolamine or tacrine (10.0 μMg each) was injected with a delay of 5 h after the learning trial. These results show that cholinergic manipulations aimed at the nucleus accumbens can have substantial effects in this posttrial memory paradigm, which depend on drug, dose, and time of injection, and the specific kind of behavioral measure analyzed. Among others, the findings are discussed with respect to the role of muscarinic and nicotinergic cholinergic mechanisms in the nucleus accumbens on cognitive functions. They may be relevant, for example, for understanding the psychopathology of Alzheimer's disease, since the nucleus accumbens is one of the sites where cholinergic neurons are lost in this neurodegenerative disease.