Our earlier studies have demonstrated that administration of low micrograms/kg doses of nicotine to young adult monkeys prior to a delayed matching-to-sample (DMTS) task resulted in a centrally mediated improvement in performance of the task, particularly when delay intervals which most greatly challenged the animal's capabilities were involved. The present study confirmed these findings using a completely computer driven and automated procedure. In addition, performance on the DMTS was observed to be enhanced when animals were again tested 24 h after the dose of nicotine. Further analysis of the data indicated that the majority of enhancement to nicotine could be accounted for by a greatly increased performance at the least preferred stimulus color. Position preference (left vs. right stimulus) was not a factor in nicotine-induced enhancement. Two aged monkeys (34 years old Macaca mulatta) were significantly more difficult to train in the DMTS task and their longest delay capabilities were significantly shorter than the young animals (Macaca fascicularis). Nevertheless, the aged animals were essentially similar in most respects in their responses to nicotine administration. These data are consistent with a role for central nicotinic systems in memory performance and with the ability of nicotine to produce enhancement of selective features of mnemonic strategy in young and old monkeys. Furthermore, it is possible that either model, the aged animal, or the young animal stressed to his mnemonic capability may provide a good model for learning and memory disorders in humans.

Aging↗

PubMedDate not supplied

Evaluation of two rodent delayed-response memory tasks: a method with retractable levers versus a method with closing doors.

The purpose of this study was to evaluate and compare two similar rodent memory tasks developed in our laboratory that employ stimulus discrimination and delayed response (light and tone stimuli and variable length delays) and to determine their sensitivity to the muscarinic-acetylcholine receptor (mAChR) antagonist, scopolamine hydrobromide (SCOP HBr), and its quaternary (methylbromide) analog (SCOP MBr). Male Wistar rats were trained in either an open chamber that employed retracting levers (RLM) during the delays, or a method that utilized closing doors (CDM) that separated the rats from the levers during delays to reduce positional (nonmnemonic) strategies. When the rats were well trained, dose-effect studies (microg/kg doses, s.c., 30 min before test sessions) of SCOP HBr or MBr were performed. Baseline performance was characterized by delay-dependent decreases in accuracy in both methods except when the tone was the stimulus in the RLM. SCOP HBr impaired performance in both tasks at the higher doses tested, although the effects were more consistent in the CDM task and accuracy associated with each stimulus was affected similarly. Surprisingly, SCOP MBr also impaired performance of each task, especially when the tone was the stimulus, while accuracy associated with the light was not affected in the CDM task. Overall, the results indicated that the CDM was a somewhat more reliable task, appearing to reduce positional strategies with less variability in response to the mAChR antagonists, although some stimulus-modality specific effects were noted. It also appears important to consider the peripheral effects of mAChR antagonists (and potential central effects of quaternary mAChR antagonists) when interpreting results from behavioral studies, especially those involving conditional discrimination and delayed response.

Acoustic Stimulation↗

PubMedDate not supplied

Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo.

(2.4)-Dimethoxybenzylidene anabaseine dihydrochloride (GTS-21), a compound that interacts with rat neuronal nicotinic acetylcholine receptors (nAChRs), was evaluated using human recombinant nAChRs in vitro and various pharmacokinetic and behavioral models in rodents, dogs and monkeys. GTS-21 bound to human alpha 4 beta 2 nAChR (K1-20 nM) 100-fold more potently than to human alpha 7 nAChR, and was 18- and 2-fold less potent than (-)-nicotine at human alpha 4 beta 2 and alpha 7 nAChR, respectively. Functionally. GTS-21 stimulated [5H]dopamine release from rat striatal slices with an EC50 of 10 +/- 2 microM (250-fold less potent and 70% as efficacious as (-)-nicotine), an effect blocked by the nAChR antagonist dihydro-beta-erythroidine. However, GTS-21 did not stimulate human alpha 4 beta 2 nor human ganglionic nAChRs significantly. In vivo, GTS-21 had no adverse effect on dog blood pressure (< or = 2.5 micromol/kg i.v. bolus infusion), in marked contrast with (-)-nicotine, GTS-21 (-62 micromol/kg.s.e.) also did not cross-discriminate significantly with (-)-nicotine in rats and did not reduce temperature or locomotion in mice. Neither was it active in the elevated plus maze anxiety model (0.19-6.2 micromol/kg.IP) in normal mice. However, GTS-21 did improve learning performance of monkeys in the delayed matching-to-sample task (32-130 nmol/kg.i.m.).

Animals↗

PubMedDate not supplied

Effects of concomitant cholinergic and adrenergic stimulation on learning and memory performance by young and aged monkeys.

The beneficial effects of physostigmine and other centrally acting AChE inhibitors on learning and memory processes have been documented in several studies. Some of these compounds are currently being examined for their potential in the treatment of Alzheimer's disease. However, the ability to employ this class of agents alone is limited by the potential for debilitating and dangerous side effects. In addition, a growing body of evidence also suggests a role for a number of other transmitter systems in this disorder. Agents such as clonidine that address adrenergic deficits have recently been demonstrated to enhance memory performance in monkeys. Clonidine also inhibits the function of cholinergic neurons in specific brain regions and reduces certain side effects of physostigmine. This evidence provided the impetus to evaluate a combination of physostigmine and clonidine in a learning and memory paradigm in monkeys. Seven young adult and three aged macaque monkeys performing a delayed matching-to-sample task received regimens of increasing doses of clonidine and physostigmine on separate occasions to determine the optimal dose of each agent in terms of enhanced memory performance. The optimal dose of clonidine was combined with a series of physostigmine doses and performance was compared to that using the two drugs alone. The best combination regimen of clonidine and physostigmine was more effective than either drug alone in enhancing memory performance. Part of the benefit may have been due to the ability of the animals to tolerate significantly higher doses of physostigmine in the combination regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMedDate not supplied

A 3-year prospective multicenter follow-up report on the immediate and delayed-immediate placement of implants.

A total of 264 implants was placed in 143 patients using different immediate or delayed-immediate implant placement techniques in 12 different centers participating in a prospective multicenter study. The reason for tooth extraction was evaluated; bone quality and quantity were classified; socket depths were registered; and data on implant type, size, and position were collected. One hundred thirty-nine suprastructures were placed on 228 implants in 126 patients. A follow-up evaluation was done on 125 patients after 1 year of loading and on 107 patients after 3 years of loading. Clinical parameters (bleeding or not bleeding, pocket depth, and implant mobility) were evaluated after 1 and 3 years, and the marginal bone level after 1 year of loading was measured on radiographs. Clinical comparisons were performed to evaluate implant loss in relation to implant type, size, position, bone quality and quantity, socket depth, reason for tooth extraction, and placement method. In addition, life table analysis was done for cumulative implant survival rates. There was no clinical difference with respect to socket depth or when comparing the different placement methods. A higher failure rate was found for short implants in the posterior region of the maxilla and when periodontitis was cited as a reason for tooth extraction. Mean marginal bone resorption from the time of loading to the 1-year follow-up was 0.8 mm in the maxilla and 0.5 mm in the mandible. Over a period of 3 years, the implant survival rate was 92.4% in the maxilla and 94.7% in the mandible.

Bone Density↗