Open field habituation learning is improved by nicotine and attenuated by mecamylamine administered posttrial into the nucleus accumbens.

Using the paradigm of habituation learning in the open field, we tested the effects of unilateral microinjections of the agonist nicotine (8.0, 40.0, and 80.0 microg) and the nicotine receptor antagonist mecamylamine (0.1, 1.0, 10.0 microg) into the core of the nucleus accumbens. When injected posttrial, that is, immediately after the first exposure to the open field, nicotine dose-dependently enhanced behavioral habituation during the test on the following day, indicating a facilitation of memory, whereas mecamylamine impaired habituation at the highest dose, but not at the two lower doses. When injected 5 h after the learning trial, nicotine (40 microg) and mecamylamine (10 microg) impaired habituation on the subsequent day. A control experiment did not provide evidence for possible proactive effects of mecamylamine. These findings are discussed with respect to the possible behavioral functions of cholinergic, and especially nicotinic, mechanisms in the nucleus accumbens. They may also be relevant for understanding cholinergic-linked psychopathologies such as Alzheimer's disease, since the nucleus accumbens is one of the sites where cholinergic neurons are lost in this neurodegenerative disease.

Injections of tacrine and scopolamine into the nucleus accumbens: opposing effects of immediate vs delayed posttrial treatment on memory of an open field.

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 micrograms), and the muscarinic receptor antagonist scopolamine (0.1, 1.0, 10.0 micrograms) 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 micrograms) 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 micrograms 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 micrograms 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.

Intraaccumbens injections of substance P, morphine and amphetamine: effects on conditioned place preference and behavioral activity.

The nucleus accumbens of the rat plays a critical role in behavioral activation and appetitive motivation. Within the nucleus accumbens, the shell subarea may be especially relevant, since this site is anatomically related to other brain areas that are considered to play a critical role in the processing of motivation. We investigated the behavioral effects of local drug treatments aimed at the shell of the nucleus accumbens and tested the indirect dopamine agonist d-amphetamine, the opiate agonist morphine, and the neurokinin substance P. These substances are known to exert positive reinforcing effects, and can affect behavioral activity; effects that are physiologically closely related to the nucleus accumbens and its inputs and outputs. Our results show that unilateral microinjections of amphetamine (1.0 microg, 10.0 microg) into the shell of the nucleus accumbens dose-dependently stimulated behavioral activity (locomotion, rears, sniffing), and led to conditioned place preference. Furthermore, the effect of amphetamine on place preference was negatively related to the psychomotor stimulant action on rears. Morphine injections (5.0 microg) also stimulated behavioral activity and elicited contraversive turning, but were ineffective with respect to place preference. Finally, the neuropeptide substance P, injected in a dose range of 0.1-10.0 ng, had no significant behavioral effects. These findings are discussed with respect to the role of dopaminergic, peptidergic and cholinergic mechanisms in the nucleus accumbens. It is suggested that dopamine, opiates, and neurokinins in the shell of the nucleus accumbens are differentially involved in mediating behavioral activity and appetitive motivation.

Modulation of memory, reinforcement and anxiety parameters by intra-amygdala injection of cholecystokinin-fragments Boc-CCK-4 and CCK-8s.

This series of experiments examined the effects of the cholecystokinin (CCK) fragments Boc-CCK-4 and CCK-8s on memory, reinforcement and anxiety following unilateral injection into the central nucleus of the amygdala (CeA). In experiment 1, rats with chronically implanted cannulae were injected with CCK-8s or Boc-CCK-4 and were tested on a one-trial uphill avoidance task. Post-trial injection of 20 ng Boc-CCK-4 or 1 ng CCK-8s was found to improve the retention performance, whereas lower and higher doses had no effect. The hypermnestic effects of Boc-CCK-4 and CCK-8s were no longer evident when injection was performed 5 h, rather than immediately, after the learning trial. In experiment 2, the elevated plus-maze was used to gauge anxiogenous properties of intra-amygdala injections of Boc-CCK-4 and CCK-8s in memory-enhancing doses. The treatment with 20 ng Boc-CCK-4 and 1 ng CCK-8s did not influence the number of entries into and time spent on the open and enclosed arms of the maze as well as other anxiety-related behaviors. In experiment 3, possible reinforcing effects of the CCK-fragments were examined. After intra-amygdala injection of Boc-CCK-4 or CCK-8s in memory-enhancing doses the rats were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. Subsequent tests for conditioned corral preference revealed no evidence for reinforcing or aversive effects of the CCK-fragments. In sum, these findings indicate that Boc-CCK-4 and CCK-8s facilitate memory processing upon injection into the CeA without exerting reinforcing or anxiogenous effects.