Long-term effects on motor activity induced by apomorphine or scopolamine after intracerebral injections of cycloheximide or glutamate shortly after hatching in chickens

Compared to controls, bilateral forebrain injections of cycloheximide or glutamate in 2-day-old chicks resulted in significantly less activity in response to intraperitoneal injections of the dopaminergic agonist, apomorphine, or the cholinergic antagonist, scopolamine, when tested on stabilimeters four weeks later. These preliminary results are consistent with the idea that amongst other effects neonatal injections of cycloheximide or glutamate may alter dopaminergic and cholinergic neurotransmitter mechanisms involved in motor behavior in birds.     

Central cholinergic interactions in somato-vegetative reflexes

In cats lightly anaesthetized with urethane (600 mg/kg, i.p.), electrical stimulation of the sciatic nerve elicited frequency-dependent pressor reflexes and contractions of the nictitating membrane. Administration of oxotremorine (0.2 mg/kg, i.v.) or physostigmine (0.5 mg/kg, i.p.) resulted in depression of the pressor reflexes. At the same time, physostigmine enhanced the reflex contractions of the nictitating membrane, while oxotremorine induced sustained contraction of the latter. All these effects were antagonized by the tertiary amine scopolamine, but not by the quaternary atropine methylbromi.The results point to a role of central cholinergic mechanisms in the integration of somato-vegetative reflexes, and give evidence that the sympathetic driving of different effectors is not uniformly organized by the central nervous system.     

Age-dependent effects of scopolamine on avoidance,locomotor activity,and rearing

In Experiment 1, 15-, 17-, 21-, 36- and 90-day-old rats were injected with either physiological saline or 0.5, 1.0, 4.0, 8.0, 16.0 or 32.0 mg/kg of scopolamine (an anticholinergic). Immediately after the injection, shuttle crossings during adaptation were recorded for 8 min, and then the rats were given a single session of 100 two-way avoidance trials. In all ages, scopolamine increased two-way avoidance and intertrial responses throughout training and avoidance and intertrial responses were positively correlated, suggesting that increased avoidance was due, in part, to increased locomotor activity. In addition, scopolamine increased locomotor activity at an earlier age in a stressful situation, i.e. during the intertrial interval, than in a less stressful environment, i.e. during adaptation. In Experiment 2, photocell crossings and rearing were examined in 15-, 17-, 21-, 36-, 90- and 275-day-old rats injected with saline or 0.5, 1.0, 4.0, 8.0 or 16.0 mg/kg of scopolamine hydrobromide. Scopolamine increased photocell crossings in rats 21 days of age and older but did not increase rearing until 36 days of age. Scopolamine also had different behavioral effects in the three oldest ages. Thus, cholinergic involvement in these behaviors changes from at least 15 to 275 days of age. Methylscopolamine, which does not cross the blood-brain barrier, did not alter the behaviors examined in Experiments 1 and 2, suggesting that development of cholinergic neurons in the CNS is responsible for the agedependent behavioral effects of scopolamine.     

Effects of transdermal scopolamine upon psychological test performance at sea

Summary The effects of transdermal scopolamine upon objective psychological performance assessments and self reports of feeling states, were investigated with volunteer subjects at sea. Scopolamine and placebo patches were administered on consecutive days in a counterbalanced order. Psychological performance was assessed 24 h following each transdermal patch. Choice reaction time and code substitution performance levels were not significantly changed, but letter cancellation errors were significantly more frequent following transdermal scopolamine. Transdermal scopolamine caused significantly more reports of dry mouth. More subjects were also unable to undertake the performance tests following scopolamine than placebo, due to difficulties in focusing on the test materials. However despite deleterious side effects with some personnel, others responded positively to the scopolamine patch. As noted by other workers, responses to the transdermal scopolamine patch seem to be quite variable.Dr. A. C. Parrott is Senior Psychologist at the Institute of Naval Medicine.Surgeon Lt. R. Jones RN, was Medical Officer to HMS Hydra     

Premedication with intramuscular dixyrazine: (Esucos®)

Ninety patients scheduled for general or orthopaedic surgical procedures were randomly assigned to receive one of three i.m. premedications: dixyrazine 0.5 mg kg-1; morphine 0.15 mg kg-1 and scopolamine 0.0065 mg kg-1; or placebo. The premedication was administered and evaluated in a double-blind fashion. The patients were anaesthetized with thiopentone, fentanyl, pancuronium, and ventilated with nitrous oxide in oxygen. The three premedications had no noticeable anxiolytic effect. Although there was no difference in the frequency of observed postoperative nausea and vomiting between the three groups, premedication with dixyrazine nonetheless reduced the patients' experience of postoperative nausea as well as their need for postoperative antiemetics. Although patients in the two treatment groups were significantly more sedated immediately before induction of anaesthesia than patients receiving placebo, the degree of postoperative sedation was similar in all three groups. Morphine-scopolamine caused more postoperative dizziness than dixyrazine and placebo. Lack of recall was produced by both morphine-scopolamine and dixyrazine. It is concluded that premedication with dixyrazine is a useful alternative, especially in patients who have previously experienced postoperative nausea and vomiting.     

Effects of d-amphetamine,Org 2766, scopolamine,and physostigmine on repeated acquisition of four-response chains in rat

Adult rats were trained to emit a different four-response sequence on three levers for food reinforcement in each daily two-hour session. Four sequences of putatively equal difficulty were used, with each sequence recurring every fourth session. Within-session errors declined as a function of practice. Most subjects showed a significant idiosyncratic sequence bias. d-amphetamine, tested at 0.1–2.0 mg/kg, increased errors as a function of dose. Org 2766 had no effect. Scopolamine and physostigmine, tested at 0.01–1.0 mg/kg, increased errors only at the highest doses, which produced tremor or ataxia. Results were generally consistent with previous results from other species. It was concluded that repeated acquisition in the rat is feasible for behavioral pharmacology and toxicology but that long training times and sequence bias limit its practicality.     

脑桥-延髓中毒蕈碱受体亚型与环核苷酸的关系(英文)

目的：研究脑桥-延髓中M受体亚型与环核苷酸的关系.方法:大鼠ip药物,脑桥-延髓等组织中cGMP和cAMP含量分别用放射免疫法和竞争性蛋白结合法测定,对照组ip生理盐水.结果:ip匹鲁卡品,脑桥-延髓中cGMP含量增加,cAMP变化不明显,ip哌仑西平或东莨菪碱可拮抗之.ip 6β-乙酰氧基去甲托烷12μg kg~(-1),脑桥-延髓中cAMP含量减少,而25 μg kg~(-1)使cAMP和cGMP均减少,ip AFDX 116或阿托品可拮抗之.结论:激动脑桥-延髓中M_1受体使cGMP增加,激动M_2受体使cGMP和cAMP减少.     

Memory-related effects of cholinergic receptor ligands in mice as measured by the elevated plus maze test

The purpose of our experiments was to examine the influence of cholinergic receptor ligands on memory-related behavior in mice using the elevated plus maze (EPM) test. The EPM test allows the exploration of different memory processes (acquisition and consolidation), depending on the time of drug treatment. The time necessary for mice to move from the opened arm to the enclosed arm (i.e., transfer latency, TL) was used as an index of memory. Our findings reveal that for both the processes of acquisition and consolidation, treatment with nicotine (0.035 or 0.175 mg/kg, free base, sc) shortened TL on the second day of the experiments (TL2), thus improving memory processes. Treatment with scopolamine (0.3 or 1.0 mg/kg, ip) significantly increased TL2 values, thus impairing cognitive processes. Moreover, we found that treatment with nicotine, at the non-effective doses used during testing, prevented scopolamine-induced memory impairment by inducing a decrease in TL2 values. Next, we evaluated the influence of bupropion (10 or 20 mg/kg, ip), a drug currently used for smoking cessation in humans, on memory-related behavior induced by treatment with nicotine and scopolamine. An acute injection of bupropion (10 or 20 mg/kg) prior to injection with either nicotine (0.035 mg/kg) or scopolamine (1.0 mg/kg) significantly prevented nicotine-induced memory improvement or scopolamine-induced memory impairment. Bupropion treatment can diminish the rewarding (dependence-producing) effects of nicotine and also the cognitive effects that are related to addiction. Our studies further indicate the great involvement of the cholinergic system in memory processes and the potential for the development of more effective pharmacotherapies for memory impairment-like human disorders in which the cholinergic pathways have been implicated.     

Cholinergic modulation of visuospatial responding in central thalamus

Central thalamus has extensive connections with basal ganglia and frontal cortex that are thought to play a critical role in sensory-guided goal-directed behavior. Central thalamic activity is influenced by cholinergic projections from mesopontine nuclei. To elucidate this function we trained rats to respond to lights in a reaction time (RT) task and compared effects of muscarinic (2.4, 7.3, 22 nmol scopolamine) and nicotinic (5.4, 16, 49, 98 nmol mecamylamine) antagonists with the GABA_A agonist muscimol (0.1, 0.3, 1.0 nmol) in central thalamus. We compared this with subcutaneous (systemic) effects of mecamylamine (3.2, 9.7, 29 µmol/kg) and scopolamine (0.03, 0.09, 0.26 µmol/kg). Subcutaneous scopolamine increased omissions (failure to respond within a 3-s response window) at the highest dose tested. Subcutaneous mecamylamine increased omissions at the highest dose tested while impairing RT and per cent correct at lower doses. Intrathalamic injections of muscimol and mecamylamine decreased per cent correct at doses that did not affect omissions or RT. Intrathalamic scopolamine increased omissions and RT at doses that had little effect on per cent correct. Anatomical controls indicated that the effects of mecamylamine were localized in central thalamus and those of scopolamine were not. Drug effects did not interact with attention-demanding manipulations of stimulus duration, proximity of stimulus and response locations, or stimulus array size. These results are consistent with the hypothesis that central thalamus mediates decisional processes linking sensory stimuli with actions, downstream from systems that detect sensory signals. They also provide evidence that this function is specifically influenced by nicotinic cholinergic receptors.