Effects Of Cholinergic Enhancement Research Articles

The effects of cholinergic enhancement and consolidation duration on perceptual learning of texture discrimination

The effects of cholinergic enhancement and consolidation duration on perceptual learning of texture discrimination

Tacrine improves reversal learning in older rats

Age-related decline has been reported in most cognitive domains, including executive function: in particular, attentional set-shifting and reversal learning, as measures of executive control, are impaired in aged populations of both humans and rats. Despite the importance of the cholinergic system in age-related cognitive decline, no data are available on the effects of cholinergic enhancement on age-related performance deficits in tests of attentional set-shifting. We investigated the effects of the cholinesterase inhibitor tetrahydroacridin-9-amine (tacrine) on reversal learning and attentional set-shifting in older rats (aged 16–21 months) using the rodent version of the intradimensional/extradimensional attentional set-shifting task in a repeated-measures design. Discrimination acquisition was not impaired, but age-related impairments in reversal learning were persistent between tests, and ameliorated by the 3 mg/kg dose of tacrine. No age-related impairments in set-shifting were seen, but there was a tendency for tacrine to reduce the cost of shifting set. Given the lack of previous evidence for a role of cortical acetylcholine in attentional set-shifting tasks, it is likely that altered neurotransmitter interactions in striatum underlie this improvement.

Effects of cholinergic enhancement on voluntary and involuntary visuospatial attention in humans

Effects of cholinergic enhancement on voluntary and involuntary visuospatial attention in humans

Cholinergic modulation of visual working memory during aging: A parametric PET study

Age-related differences in the regional recruitment of prefrontal cortex (PFC) during cognitive tasks suggests that aging is associated with functional reorganization. Cholinergic enhancement with physostigmine reduces activity in the PFC regions selectively recruited during working memory (WM) and increases activity in visual processing areas, suggesting that augmenting cholinergic function reduces task effort by improving the visual representation of WM stimuli. Here, we investigated how cholinergic enhancement influenced PFC and visual cortical activity in young and older subjects as WM difficulty was altered. Regional cerebral blood flow (rCBF) was measured using H 2 15O-PET in 10 young and 10 older volunteers during a parametrically varied face WM task, following an i.v. infusion of saline and physostigmine. Reaction time decreased during physostigmine relative to placebo in both groups. Prefrontal brain regions selectively recruited in each age group that responded differentially to task demands during placebo, had no significant activity during physostigmine. Medial visual processing areas showed task-selective increases in activity during drug in both groups, while lateral regions showed decreased activity in young and increased activity in older participants at longer task delays. These results are consistent with our previous findings, showing that the modulatory role of the cholinergic system persists during aging, and that the effects of cholinergic enhancement are functionally specific rather than anatomically specific. Moreover, the use of the parametric design allowed us to uncover group specific effects in lateral visual processing areas where increasing cholinergic function produced opposite effects on neural activity in the two age groups.

EFFECTS OF THE SELECTIVE ACETYLCHOLINESTERASE INHIBITOR TAK-802 ON THE VOIDING BEHAVIOR AND BLADDER MASS INCREASE IN RATS WITH PARTIAL BLADDER OUTLET OBSTRUCTION

We examined the effects of the selective acetylcholinesterase (AChE) inhibitor TAK-802 on voiding behavior and residual urine volume in rats with partial bladder outlet obstruction (BOO) vs rats treated with the nonselective AChE inhibitor distigmine and the muscarinic agonist bethanechol. In addition, the effect of repeat doses of TAK-802 on the bladder mass increase associated with BOO was also examined. Male rats with BOO were used. Six to 8 days after obstruction voiding behavior was observed in a metabolic cage. The animals were then treated orally with 1 drug, and voiding frequency and urine volume at each void were measured for 3 hours. Subsequently the volume of urine retained in the bladder (residual urine) was measured. In another experiment bladder weight in rats with BOO was measured after early repeat doses of TAK-802. BOO increased voiding frequency and decreased average voided volume. TAK-802 and distigmine increased average voided volume, while not causing any change in voiding frequency. On the other hand, bethanechol increased voiding frequency without affecting average voided volume. While all 3 drugs significantly decreased residual urine volume, TAK-802 was most efficacious. In addition, bladder weight in the control BOO group was greater (approximately 2.2-fold) than that in the sham operated group and early repeat administration of TAK-802 prevented the bladder mass increase. AChE inhibitors decreased residual urine volume by restoring voiding function in rats with BOO, although only the effect of TAK-802 was dose dependent. Bethanechol also decreased residual urine volume in a dose dependent manner but by increasing voiding frequency. The prevention of a bladder mass increase by TAK-802 treatment may be attributable to its effect on restoring voiding.

Effects of cholinergic enhancement on working memory (WM) performance and prefrontal cortex (PFC) activity in young and older healthy subjects

Effects of cholinergic enhancement on working memory (WM) performance and prefrontal cortex (PFC) activity in young and older healthy subjects

Effect of cholinergic enhancement by pyridostigmine on growth hormone secretion in obese adults and children

In obesity the reduced growth hormone (GH) responses to several provocative stimuli including growth hormone-releasing hormone (GHRH) indicate a diminished somatotroph responsiveness but do not distinguish between primary pituitary and hypothalamic pathogenesis. However, it has been shown that the cholinergic system positively influences GH secretion likely by modulating somatostatin release in a negative way. Thus, the effect of cholinergic activity enhancement by pyridostigmine (PD), an acetylcholinesterase inhibitor, on both basal and GHRH-induced GH secretion was studied in 14 obese subjects (eight adults and six children). Eighteen nonobese subjects (seven adults and 11 children) were studied as controls. In obese subjects the GHRH-induced GH increase was lower than in controls (peak, mean ± SEM, adults, 9.2 ± 2.7 v 16.8 ± 5.7 ng/mL; children, 8.0 ± 0.8 v 20.3 ± 4.6 ng/mL) attaining statistical significance only in children group ( P < .02). The PD-induced GH response in the two obese groups was similar to that observed in relative controls (adults, 5.3 ± 1.0 v 7.4 ± 1.7 ng/mL; children, 9.6 ± 1.6 v 13.3 ± 1.4 ng/mL). PD clearly potentiated the GH response to GHRH in obese subjects, both adults ( P < .05 v GHRH alone) and children ( P < .0005 v GHRH alone). However, the GH response to PD + GHRH was significantly reduced in obese subjects compared with controls (adults, 18.1 ± 2.2 v 42.7 ± 10.7 ng/mL, P < .05; children, 28.3 ± 4.5 v 58.2 ± 7.7 ng/mL, P < .01). In conclusion, PD is able to potentiate the blunted GH response to GHRH in obese adults and children, inducing a GH increase similar to that observed after GHRH alone in normal subjects. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in obesity. However, considering that in obese subjects the PD + GHRH-induced GH response is lower than that observed in normals, these data suggest a coexisting primary pituitary impairment.

GROWTH HORMONE RESPONSES TO PYRIDOSTIGMINE IN NORMAL ADULTS AND IN NORMAL AND SHORT CHILDREN

There is evidence indicating that the cholinergic system positively modulates GH release probably by inhibiting somatostatinergic tone. In the present study, the effects of cholinergic enhancement by pyridostigmine, (PD), a cholinesterases inhibitor, on GH release in normal adults (n = 14) (NA) and in both normal (n = 5) (NC) and short children (n = 19) (SC) with familial short stature (n = 7) or constitutional growth delay (n = 12) were studied. In SC the insulin hypoglycaemia (IH)-induced GH increase was also studied. In both NC and SC 60 mg orally PD induced a significant GH increase with mean peak at 90 min (mean +/- SEM 11.0 +/- 2.2 ng/ml in NC and 11.2 +/- 2.3 ng/ml in SC). The GH areas under response curve (AUC) were 379.3 +/- 76.6 and 327.8 +/- 43.2 ng/ml/h in NC and SC respectively. In NA 120 mg orally PD induced a significant GH increase with mean peak at 120 min (5.1 +/- 1.1 ng/ml) which was significantly lower (P less than 0.05) than that observed in both NC and SC. This statistical difference was strengthened by evaluating AUC (NA:205.6 +/- 33.7 ng/ml/h, P less than 0.05 vs NC and SC). The correlation of drug dosage with body area ruled out that this difference could be related to the different PD dose in adults and children. In SC, IH induced a GH increase significantly lower than that observed after PD (GH peak 7.8 +/- 0.6 vs 16.4 +/- 1.9 ng/ml P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)