Nicotine enhances stimulus detection performance of middle- and old-aged rats: a longitudinal study.

The effects of nicotine on sustained attention were tested in F344xBN male rats when they were chronologically middle and old aged. The rats (n = 11) were trained in a two-choice, stimulus detection task in which a press of one of two levers was reinforced with food, with the correct lever indicated by the position of a briefly illuminated light. They were tested when they were 24-25 and 34-35 months of age (i.e., at 60-68% and 85-95%, respectively of their expected median life span) after saline or 0.1-0.5 mg/kg doses of nicotine (SC). A significant dose-related improvement in percent correct choices and decrease in choice response times was found at both ages, and there was no significant main effect of age or an age by dose interaction. These results support the position that nicotine can enhance attentional processes in rats throughout their life span. Nicotine and other nicotinic agonists may have efficacy in the treatment of disorders such as Alzheimer's disease.

Pfiesteria toxin and learning performance.

Pfiesteria piscicida is an estuarine dinoflagellate involved with fish kills along the east coast of the United States. We previously documented a radial-arm maze learning deficit in rats exposed to Pfiesteria that may be related to cognitive deficits seen in humans after accidental Pfiesteria exposure. The current study elucidated important behavioral parameters of this deficit. There were six dose groups. Forty (10/group) adult female Sprague-Dawley rats were injected (s.c.) with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600, 106,800, or 320,400 Pfiesteria cells/kg of rat body weight or a cell-free filtrate of the 106,800 cells/kg dose). One control group (N = 10) was injected with saline and one (N = 10) with aquarium water not containing Pfiesteria. Half of the rats in each group were tested on an 8-arm radial maze in a standard test room, and the other half were tested on the radial maze in a sound-attenuating chamber. In the standard maze room, there was a significant effect of Pfiesteria (p < 0.05) impairing choice accuracy improvement over the first six sessions of training among rats administered 106,800, 320,400, and the 106,800 cells/kg filtered sample. In contrast, there was no indication of an effect of Pfiesteria when the rats were tested on the same configuration radial maze in the sound-attenuating chamber. After 18 sessions of training in one room, the rats were switched for six sessions of testing in the other room and finally were switched back to their original room for three sessions. There was a significant Pfiesteria-induced deficit when the rats were tested in the standard test room but not when they were tested in the sound-attenuating chamber. When the Pfiesteria-exposed rats were initially switched from the sound-attenuating chamber to the standard test room they performed significantly worse than controls, whereas Pfiesteria-treated rats switched from the standard test room to the sound-attenuating chamber did not perform differently from controls. These results suggest that the Pfiesteria-induced learning impairment may result from the negative impact of distracting stimuli. At the time of the learning impairment, no overt Pfiesteria-related effects were seen using a functional observational battery and no overall response latency effects were seen, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the initial use of the figure-8 maze in this line of research, the rats in the same Pfiesteria treatment groups that showed significant deficits in the radial-arm maze showed greater declines in activity rates in a 1-h figure-8 locomotor activity test. Both the 106,800 and 320,400 Pfiesteria cells/kg groups showed significantly greater linear trends of activity decline relative to tank water-treated controls. This reflected an initial slight hyperactivity in the Pfiesteria-treated animals followed by a decrease to control levels. Pfiesteria effects in the figure-8 maze and in early radial-arm maze training may be useful in a rapid screen for identifying the critical toxin(s) of Pfiesteria in future studies.

Nicotinic acetylcholine involvement in cognitive function in animals.

Nicotinic cholinergic systems are involved with several important aspects of cognitive function including attention, learning and memory. Nicotinic cholinergic receptors are located in many regions of the brain, including areas important for cognitive function such as the hippocampus and frontal cortex. Nicotinic agonists have been found in rodent and non-human primate studies to improve performance on a variety of memory tasks. In a complementary fashion, nicotinic antagonists such as mecamylamine impair working memory function. In humans, similar effects have been seen. Nicotinic agonist treatment can improve attention, learning and memory and nicotinic antagonist treatment can cause deficits. To define the neural substrates of nicotinic involvement in cognitive function, three areas of investigation are underway. 1) Critical neuroanatomic loci for nicotinic effects are beginning to be determined. The hippocampus, frontal cortex and midbrain dopaminergic nuclei have been found to be important sites of action for nicotinic involvement in memory function. 2) Nicotinic receptor subtype involvement in cognitive function is being studied. There has been considerable recent work identifying nicotinic receptor subunit conformation including alpha and beta subunits. Nicotinic receptor subtypes appear to be associated with different functional systems; however, much remains to be done to determine the precise role each subtype plays in terms of cognitive function. 3) Nicotinic interactions with other transmitter systems are being assessed. Nicotine receptors interact in important ways with other systems to affect cognitive functioning, including muscarinic ACh, dopamine, norepinepherine, serotonin, glutamate, and other systems. Nicotinic function in clinical populations and potential for therapeutics has been investigated for Alzheimer's disease, Parkinson's disease, schizophrenia and attention deficit/hyperactivity disorder. Areas which need to receive greater attention are the exact anatomical location and the specific receptor subtypes critically involved in nicotine's effects. In addition, more work needs to be done to develop and determine the efficacy and safety of novel nicotinic ligands for use in the long-term treatment of human cognitive disorders.

Young children's understanding of briefly versus extremely delayed images of the self: emergence of the autobiographical stance.

Eighty-eight young 3-, 4-, and 5-year-olds were scheduled for 2 testing sessions. On Visit 1, the children were videotaped playing a game while an experimenter covertly placed a large sticker on their head and covertly removed it after the game. One week later, the children were videotaped playing a different game. A sticker was again covertly placed on their heads. Half the children in each age group then observed the video from the previous week, whereas the other half observed the tape from 3 min earlier. Less than half of the 3-year-olds in both conditions reached up for the sticker. In contrast, the majority of 4- and 5-year-olds in the briefly delayed condition reached for the sticker, but few in the extremely delayed condition did so. By 4 years of age, children may have developed a causal understanding of the self's endurance through time.

Facilitation of stimulus detection performance of rats with d-amphetamine: a function of dose and level of training.

Conditions under which amphetamine may facilitate stimulus detection task choice performance in rats were investigated. Rats (n=15) were trained in a two-choice, light-detection task to three successively more stringent criterion levels of task training (minimal, intermediate, and extended) and then tested after administration of saline, 0.25, 0.50, and 0.75 mg/kg d-amphetamine (AMP). For each training level, baseline levels of choice accuracy were maintained at approximately 82% by manipulating the animals' cue duration. No aspect of performance was enhanced by any dose of AMP after minimal criteria training, and there was a dose-dependent decrease in the number of trials completed. After the intermediate level of training, the 0.25 mg/kg dose of AMP reliably increased choice accuracy, there was no reliable change in choice reaction time, and there was a dose-dependent decrease in the number of trials completed. After the extended training, the 0.25 mg/kg dose of AMP reliably increased choice response accuracy, the 0.25 and 0.50 mg/kg doses of AMP reliably decreased choice reaction time, and there was no reliable change in the number of trials completed at any dose of AMP. These results support the contention that psychostimulants can facilitate the choice performance of rats in stimulus detection tasks if an appropriately low dose is used and the animal's behavior is strongly controlled by the stimulus-reinforcement contingencies of the task.

Differential effects of d-amphetamine on vigilance in younger and older male rats.

After training to comparable levels of performance on a two-choice, discrete-trial vigilance task, younger (9 mo) and older (26 mo) male F344xBN rats were tested after SC injections of d-amphetamine (0.125, 0.25, 0.50, and 1.0 mg/kg). Relative to their saline treatment performance levels, both groups exhibited decreases in choice latencies under the lower doses of amphetamine and an increase in food retrieval latencies after 1.0 mg/kg amphetamine. The percentage of correct responses in the older animals was lower than in the younger animals at all doses of amphetamine, and the groups differed significantly at the 0.25 and 0.50 mg/kg doses. There were no significant differences between the groups in either of the latency measures at any of the doses of amphetamine. These results suggest, as has been demonstrated with cocaine, that the alertness-altering properties of amphetamine are qualitatively different in older and younger adult organisms.