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PubMed1997

Intrastriatal injection of a muscarinic receptor agonist and antagonist regulates striatal neuropeptide mRNA expression in normal and amphetamine-treated rats.

Systemic administration of the muscarinic receptor antagonist, scopolamine, augments, whereas the muscarinic receptor agonist, oxotremorine, attenuates behaviors (locomotion and stereotypies) and preprodynorphin (PPD) and substance P (SP) gene expression in striatonigral neurons induced by the indirect dopamine receptor agonist, amphetamine (AMPH). In contrast, systemic scopolamine blocks, whereas oxotremorine augments, AMPH-stimulated preproenkephalin (PPE) gene expression in striatopallidal neurons. This study investigated the site of action of these effects by administering scopolamine and oxotremorine directly into the striatum and assessing the expression of neuropeptide mRNAs with quantitative in situ hybridization. Unilateral injection of scopolamine into the dorsal striatum augmented, and oxotremorine attenuated, AMPH (2.5 mg/kg, i.p.)-stimulated behaviors. Intrastriatal scopolamine at a concentration of 62 mM, but not 6.2 mM, increased basal levels of PPD and SP mRNAs in the dorsal striatum. In addition, both 6.2 and 62 mM scopolamine significantly augmented AMPH-stimulated PPD and SP mRNA levels. Intrastriatal infusion of 1.6 or 8.1 mM oxotremorine did not alter basal levels of striatal PPD and SP mRNAs. However, both concentrations of oxotremorine completely blocked AMPH-stimulated SP mRNA and oxotremorine at 8.1 mM blocked AMPH-stimulated PPD mRNA. In contrast, PPE induction by AMPH was blocked by 62, but not 6.2, mM scopolamine. Both concentrations of oxotremorine tended to augment basal and AMPH-stimulated PPE mRNA in the dorsal striatum but the trend was not significant. These data demonstrate an inhibition of striatonigral, and facilitation of striatopallidal, gene expression through activation of local striatal muscarinic receptors, which is consistent with the changes seen after systemic administration of muscarinic agents. Therefore, muscarinic cholinergic regulation of basal and stimulated expression of neuropeptide mRNA is processed within the striatum.

Amphetamine↗
PubMed1992

The effects of p-chlorophenylalanine-induced serotonin synthesis inhibition and muscarinic blockade on the performance of rats in a 5-choice serial reaction time task.

The effects of serotonergic dysfunction induced by treatment with p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, and cholinergic dysfunction induced by scopolamine on the performance of adult rats in the 5-choice serial reaction time task measuring selective attention were studied. Food-deprived rats were trained to detect and respond to brief flashes of light presented randomly in one of five locations, until they reached a stable level of performance (about 4 months). Scopolamine 0.2 mg/kg produced a marked variation in the performance but did not, however, induce any consistent impairment in the discriminative accuracy. Other doses of scopolamine (0.05 and 0.1 mg/kg) or N-methyl-scopolamine 0.2 mg/kg, a peripheral muscarinic receptor antagonist, did not affect discriminative accuracy. Furthermore, scopolamine as well as N-methyl-scopolamine produced a number of other performance deficits, such as significantly decreased overall probability of responding and significantly increased response latencies. PCPA treatment induced an almost total depletion (> 99%) of frontal cortical serotonin and its major metabolite 5-HIAA and reduced the frontal cortical concentrations of noradrenaline (-30%) and dopamine (-42%). During baseline testing conditions, there was a trend for the discriminative accuracy to be decreased by PCPA, although this effect failed to reach significance (P = 0.07). Presenting the stimuli at unpredictable intervals or reducing the intensity of the visual stimulus impaired discriminative accuracy in both PCPA-treated and control rats. The decrease in discriminative accuracy induced by PCPA reached statistical significance when the stimuli were presented faster than normally or the intensity of the visual stimulus was reduced. PCPA treatment did not make the rats more susceptible to the effects of scopolamine on discriminative accuracy. However, PCPA treatment also induced a number of other performance deficits, resulting in a decreased overall tendency to respond. In summary, there is a statistically non-significant trend for the discriminative accuracy to be decreased by PCPA treatment under normal testing conditions, and as the discrimination task is made more difficult (stimulus intensity reduction, presentation of the stimuli at faster than normal rates), the deficit in discriminative accuracy produced by PCPA treatment is revealed. The results suggest a role for brain serotonin in the general organization of behavior.

Animals↗
PubMed1990

Evidence for GABA-BZ receptor modulation in short-term memory passive avoidance task paradigm in mice.

The possible involvement of gamma-aminobutyric acid/benzodiazepine (GABA-BZ) receptor modulation in scopolamine-induced short-term memory deficit was investigated in mice. Passive avoidance step-down task behavior was observed. Latency of mice to reach shock-free zone (SFZ) and number of mistakes the animal made in 15 min were used as separate parameters for acquisition and memory retention, respectively. Scopolamine (0.3 mg/kg) caused a delay in reaching SFZ and an increased number of mistakes. Physostigmine reversed the scopolamine-induced increase in number of mistakes; however, it caused a delay in the time to reach SFZ. Subeffective dose of GABA, when combined with physostigmine, further delayed the latency to reach SFZ, but reduced the number of mistakes very significantly. GABA (50, 75 and 100 mg/kg, i.p.) and GABA agonists sodium valproate (30 and 60 mg/kg, i.p.), fengabine (5 and 10 mg/kg, i.p.), (+/-)baclofen (0.25, 0.5 and 1.0 mg/kg, i.p.) and (-)baclofen (0.25 and 0.5 mg/kg i.p.) reversed the scopolamine-induced effect; however, sodium valproate at higher dose delayed time to reach SFZ. Combined administration of lower dose (+/-)baclofen and subeffective dose of GABA showed significant decrease in latency and number of mistakes in scopolamine-treated animals. The specific benzodiazepine antagonist flumazenil (Ro-15-1788) (5 and 10 mg/kg, i.p.) and inverse agonist FG-7142 (10 mg/kg, i.p.) very significantly reversed scopolamine-induced increase in number of mistakes, but Ro-15-1788 failed to show any effect on latency per se and in scopolamine-treated experiments, as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Mechanisms of antimotion sickness drugs.

UNLABELLED: Eight subjects, male and female, were rotated using the step method to progressively increase the speed of rotation (+2 rpm) after every 40 head movements to a maximum of 35 rpm. The end-point for motion sickness was the Graybiel Malaise III total of symptoms short of frank nausea. The drug treatments were placebo, scopolamine 0.6 mg and 1 mg, scopolamine 0.6 mg/d-amphetamine 10 mg, scopolamine 1 mg/d-amphetamine 10 mg and amphetamine 10 mg. RESULTS: Scopolamine increased tolerated head movements over placebo level by +81, scopolamine 1 mg + 183, d-amphetamine + 118, scopolamine 0.6/d-amphetamine + 165, and scopolamine 1 mg/d-amphetamine 10 mg + 201. DISCUSSION: The drugs effective in preventing motion sickness are divided into those with central acetylcholine blocking activity and those which enhance norepinephrine activity. A combination of both of these actions produces the most effective antimotion sickness medications. CONCLUSIONS: The balance between the acetylcholine and norepinephrine activity in the CNS appears to be responsible for motion sickness.

Adult↗
PubMed1996

Regulatory effect of danggui-shaoyao-san on central cholinergic nervous system dysfunction in mice.

Since administration of a powdered extract (TSS) of Danggui-Shaoyao-San (Toki-shakuyaku-san in Japanese) alone to naive mice had no influence on ACh levels in the brain, the present study examined the effect of TSS on the central cholinergic nervous system using mice treated with scopolamine (0.5 mg/kg) or mecamylamine (0.05 mg/kg), which affects the cholinergic nervous system. TSS was suspended in a 5% carboxymethylcellulose solution and mice were orally given single or repeated (twice a day, for 14 days) administration of TSS at 50 or 500 mg/kg. Results on spontaneous locomotor activity showed that (1) single administration of TSS at 50 or 500 mg/kg to naive mice significantly inhibited vertical and horizontal locomotor activities, while repeated administration of TSS at 50 mg/kg significantly stimulated both activities; (2) in mice treated with scopolamine, repeated administration of TSS at 500 mg/kg significantly inhibited the scopolamine-induced increase in locomotor activities, whereas in mice treated with mecamylamine, single or repeated administration of TSS at 50 and 500 mg/kg did not show any influence on the mecamylamine-induced decrease in locomotor activities. Regarding the step-down passive avoidance responses; single administration, but not repeated administration, of TSS at 50 and 500 mg/kg significantly inhibited scopolamine-induced shortening of step-down latency. In mice treated with mecamylamine, TSS did not exert any influence on the step-down latency. As for ACh contents, single or repeated administration of TSS at 50 or 500 mg/kg to naive mice had no influence on the levels of ACh in the cerebral cortex, corpus striatum or hippocampus. However, the levels of brain ACh in mice treated with scopolamine showed a decrease and a single administration of TSS at 500 mg/kg significantly inhibited this scopolamine-induced decrease in ACh levels. These results indicate that TSS ameliorates dysfunction of the central cholinergic nervous system and scopolamine-induced decrease in ACh levels in mouse brain, but has no influence on ACh levels in naive mice. Thus, it suggests that TSS may be a useful therapeutic agent in Alzheimer's disease and senile dementia.

Acetylcholine↗
PubMed1986

Effects of muscarinic receptor antagonism upon two forms of stress-induced analgesia.

The present study assessed in rats the effects of muscarinic receptor antagonism upon analgesia induced by cold-water swims (CWS: 2 degrees C for 3.5 min) and 2-deoxy-D-glucose (2DG: 600 mg/kg). First, CWS analgesia was significantly reduced 30 min after the swim by scopolamine (0.01 and 0.1 mg/kg) and methylscopolamine (10 mg/kg) pretreatment, and was eliminated 60 min after the swim by scopolamine (0.01-10 mg/kg) and methylscopolamine (1,10 mg/kg) pretreatment. In contrast, scopolamine potentiated CWS hypothermia. Second, while scopolamine (1 mg/kg) and methylscopolamine (1,10 mg/kg) pretreatment prolonged 2DG analgesia, both antagonists dose-dependently reduced 2DG hyperphagia. Third, the changes in analgesic and hypothermic stress responses were not due to baseline shifts in jump thresholds or body temperatures. However the dose-dependent reductions by scopolamine and methylscopolamine in baseline food intake and 2DG hyperphagia were significantly correlated. Fourth, the dose-dependent reduction by scopolamine and methylscopolamine of pilocarpine analgesia differed in pattern from the other analgesic effects, suggesting heterogeneity in muscarinic receptor modulation of different analgesic responses.

Acetylcholine↗
PubMed1975

Motor effects of cholinergic stimulation of the globus pallidus in rats.

Forty-seven rats were cannulated permanently in either the globus pallidus or neostriatum and subsequently injected with carbachol, scopolamine, or carbachol plus scopolamine. The injection of carbachol (1 mug) into the globus pallidus produced transient hyperkinetic phasic dyskinesias (84%) followed in some cases by ipsilateral circling (47%) associated with hypertonic contralateral hind limbs. This condition progressed in some rats to a cataleptic state (42%). The injection of scopolamine (50 mug) or scopolamine (50mug) plus carbachol (1 mug) into the pallidum produced ipsilateral circling associated with hypotonia of the contralateral hind limb in a few rats. No hyperkinetic dyskinesias nor catalepsy were produced by these injections. The injection of carbachol (1 mug) into the neostriatum produced hyperkinetic dyskinesias (86%) of long duration, minimal circling (both directions) (10%), and catalepsy (29%). These effects were blocked by the addition of 50 mug of scopolamine to the carbachol injection. Scopolamine (50-100 mug) alone produced no effects after injection into the caudate/putamen. Saline injections in the neostriatum or globus pallidus produced no motor disturbance.

Animals↗
PubMed2005

Blockade of muscarinic acetylcholine receptors in the ventral tegmental area disrupts food-related learning in rats.

RATIONALE: Stimulation of ventral tegmental area (VTA) muscarinic acetylcholine receptors (mAChRs) is implicated in feeding. OBJECTIVE: To investigate the effects of mAChR blockade in the VTA on food-related learning. METHODS: In experiment 1, rats (N=12) were placed in chambers containing food and received microinjections of 0 or 5 microg/0.5 microl scopolamine prior to the first four feeding sessions and the alternate dose prior to the tenth feeding session. In experiment 2 (N=9), the effects of daily microinjections of scopolamine on lever pressing under a progressive ratio schedule of food reinforcement were tested. In experiment 3 (N=34), the effects of daily microinjections of scopolamine on lever pressing maintained by conditioned reward were investigated. RESULTS: In experiment 1, all rats demonstrated low consumption during session 1. However, pellet consumption for rats initially pretreated with the 0-microg dose rose to and stayed at maximal levels for the remaining sessions, even when pretreated with the 5-microg dose during the tenth session. Pellet consumption for rats initially pretreated with the 5-microg dose remained low, even for the first two sessions following the cessation of scopolamine pretreatment, and gradually rose to maximal levels by the eighth session. In experiment 2, scopolamine significantly decreased break points. In experiment 3, scopolamine failed to significantly decrease responding specifically on the lever producing the conditioned reward. CONCLUSIONS: Altogether, these data suggest that VTA mAChR stimulation is involved in feeding and food-related learning but may not be involved in responding maintained by conditioned reward.

Animals↗
PubMed2006

Blockade of muscarinic acetylcholine receptors in the ventral tegmental area prevents acquisition of food-rewarded operant responding in rats.

RATIONALE: We recently found that muscarinic receptor (mAChR) stimulation in the ventral tegmental area (VTA) is involved in the acquisition of a feeding task. OBJECTIVE: To investigate the involvement of VTA mAChR and nicotinic receptors (nAChR) in the acquisition and performance of a food-rewarded lever-pressing task. METHODS: In experiment 1 (N=54), rats were trained under a fixed ratio 1 schedule of reinforcement and received bilateral intra-VTA microinjections of scopolamine (0, 2.5 or 5 microg/0.5 microl) or mecamylamine (0, 5 or 10 microg/0.5 microl) before each of the first four sessions. Before session 10, all rats that initially received a dose of either compound now received the vehicle and vice versa. In experiment 2 (N=14), rats were tested with scopolamine or mecamylamine while lever pressing under a progressive ratio schedule of reinforcement. RESULTS: In experiment 1, lever pressing by rats initially treated with any mecamylamine dose or the scopolamine vehicle rose to and stayed at maximal levels for the remaining sessions. Responding by rats initially treated with the 2.5- or 5-microg dose of scopolamine remained low, even after the cessation of scopolamine treatment, and gradually rose to maximal levels by the final sessions. Injections of scopolamine 1 to 2 mm dorsal to the VTA had no significant effect on responding. In experiment 2, neither of the compounds significantly affected break points. CONCLUSIONS: Stimulation of VTA mAChR, but not of nAChR, is necessary for the acquisition of a food-rewarded lever-pressing task and neither is necessary for the performance of the task.

Animals↗
PubMed1997

Purine modulation of dizocilpine effects on spontaneous alternation.

The Y-maze was used to assess spontaneous alternation behaviour in mice to examine possible interactions between the N-methyl-D-aspartate receptor channel blocker dizocilpine and purine receptor agonists and antagonists. Scopolamine reduced spontaneous alternation. Dizocilpine also produced a dose-dependent reduction in alternation scores, which was accompanied by an increase in locomotion. The selective A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) had no effect when administered alone, or in combination with scopolamine. However, when co-administered with dizocilpine, CPX reversed both the deficit in alternation behaviour and also the increase in locomotion induced by dizocilpine. The A1 selective agonist N6-cyclopentyladenosine (CPA) had no effect on either locomotion or alternation scores when administered alone, but in combination with scopolamine, CPA attenuated the scopolamine-induced deficit. CPA had no significant effect on the dizocilpine-induced deficit. The A2 selective agonist N6-[2-(3, 5-dimethoxyphenyl)-2(2-methylphenyl)-ethyl]adenosine (DPMA), had no effect on spontaneous alternation when administered alone, but did cause a depression of locomotion. DPMA had no significant effect when co-administered with scopolamine, but reversed the deficit in spontaneous alternation, and the increase in locomotion induced by dizocilpine. The A2 selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect when given alone or in combination with scopolamine, but when co-administered with dizocilpine, DMPX reversed the reduction in spontaneous alternation caused by dizocilpine. It is concluded that dizocilpine has a detrimental effect on spontaneous alternation which is mediated partly by A1 and A2 adenosine receptors.

Adenosine↗
PubMed1985

Effect of chronic lithium on cholinergically mediated responses and [3H]QNB binding in rat brain.

Lithium (Li) has been previously reported to increase acetylcholine turnover and release in rat brain and to potentiate the neurotoxicity of cholinergic agents. We studied the effect of chronic Li administration, alone and in combination with the muscarinic antagonist, scopolamine, on two cholinergically-mediated responses and on muscarinic cholinergic receptor (MCR) binding in rat brain. Administered separately, Li and scopolamine enhanced the cataleptic and hypothermic responses to pilocarpine; combined administration resulted in an additive effect on both these measures. [3H]Quinuclidinyl benzilate ([3H]QNB) binding was increased by Li in the corpus striatum but not in the cortex, hippocampus and hypothalamus. Scopolamine increased [3H]QNB binding in the striatum, cortex and hippocampus; Li and scopolamine effects on striatal MCR were not additive. Contrary to a previous report, antagonist-induced MCR supersensitivity was not prevented by concurrent Li administration in any of the brain areas studied. The additive effect of Li and scopolamine on pilocarpine-induced catalepsy and a trend in this direction for pilocarpine-induced hypothermia suggest that the actions of the two agents to enhance cholinergically mediated responses may be achieved by different mechanisms. Supersensitive responses following scopolamine may be attributed to antagonist-induced up-regulation of postsynaptic muscarinic receptors as demonstrated in the binding studies. The effects of Li to enhance cholinergically-mediated catalepsy and hypothermia are interpreted as extending previous reports that Li stimulates brain cholinergic function by a presynaptic increase in acetylcholine turnover and release.

Animals↗
PubMed1995

Dependence of rat vertex auditory evoked potentials on central muscarinic receptor activation.

Auditory evoked potentials (AEPs) were recorded epidurally at vertex in the freely moving rat, yielding the prominent components P18 and N40 from the average waveform. Both components were severely attenuated at tone presentation rates faster than 1 Hz. Dependence of the vertex AEP on central cholinergic activation was assessed by comparing the effects of subcutaneous injections of the muscarinic antagonist scopolamine (0.1-1.0 mg/kg) to methyl-scopolamine (0.5, 1.0 mg/kg) to test for peripheral effects. Scopolamine produced a significant decrease in amplitude for both the P18 and N40 components in overall tests. N40 amplitude also showed a significant decrease at each dose of scopolamine, and the magnitude of the amplitude decrement was dose dependent. At 23 h after scopolamine, only N40 amplitude remained significantly depressed. There were no effects of injection of saline, or of methyl-scopolamine. These results confirm that middle-latency vertex AEPs in the rat are attenuated by central muscarinic receptor blockade, consistent with previous findings in cats.

Animals↗
PubMed1979

Evidence that a nigral gabaergic--cholinergic balance controls posture.

The intranigral injection of kainic acid (k.a.) (3.5 nM/s.n.) produced a lesion which resulted in a decreased muscarinic receptor binding capacity and in a decreased choline acetyl transferase (CAT) activity confined to the pars reticulata. The unilateral, intranigral injection of carbachol in the substantia nigra (s.n.) produced turning, ipsilateral to the injected side, of dose-related intensity, which was antagonized by scopolamine given either i.p. or intranigrally together with carbachol. The bilateral, intranigral injection of carbachol produced rigid catalepsy, highly resistant to apomorphine administration and antagonized by scopolamine. On the other hand, the catalepsy produced by intranigral picrotoxin was much more sensitive to apomorphine and was disrupted by systemic scopolamine administration. Intranigral scopolamine per se produced either contralateral turning or stereotyped movements consistently, when injected unilaterally or bilaterally, respectively. In addition, scopolamine injected bilaterally in the s.n. but not in the caudate nucleus (c.n.), at the concentration of 64 nM side, was able to antagonize the haloperidol-induced catalepsy and to prevent the tremors and the muscular rigidity produced by arecoline. This effect of scopolamine was surmountable with a higher dose of arecoline. Finally, intranigral muscimol (0.44 nM/s.n.) prevented the occurrence of the parkinsonian syndrome produced by systemic arecoline. It is concluded that the muscarinic receptors present in the s.n. pars reticulata play a role in the control of posture opposite to that of the nigral GABA receptors.

Animals↗
PubMed1988

Cholinergic drug effects on antidepressant-induced behaviour in the forced swimming test.

The contribution of anticholinergic effects to the action of desipramine and nomifensine was investigated in the forced swimming test in rats. The immobility time was reduced by high doses of atropine (10-25 mg/kg i.p.) and scopolamine (1.5 mg/kg i.p., 1 and 0.5 h before the test, respectively) and was unaffected by physostigmine (0.25-0.5 mg/kg i.p., 1 h before the test). Unlike atropine (25 mg/kg), scopolamine (1.5 mg/kg) increased motor activity (open-field). The anti-immobility effect of i.p. desipramine (20 or 30 mg/kg) and nomifensine (2.5 or 5 mg/kg), administered 24, 5 and 1 h before the test, was potentiated by scopolamine (0.5-1.0 mg/kg) and antagonized by physostigmine (0.25-0.5 mg/kg). The brain levels of desipramine and nomifensine were unaffected by scopolamine or physostigmine. Motor performance was impaired in rats treated with physostigmine and desipramine whereas hypermotility was observed in rats treated with scopolamine and nomifensine. The anti-immobility effect of atropine (25 mg/kg) and scopolamine (1.5 mg/kg) was not antagonized by physostigmine (0.5 mg/kg). These results indicate that anticholinergic mechanisms alone are not sufficient to influence immobility time and suggest that the cholinergic system may control, the neural circuitry upon which desipramine and nomifensine act to reduce immobility time.

Animals↗
PubMed1994

Visual discrimination and P300 are affected in parallel by cholinergic agents in the behaving monkey.

We studied the acute effect of cholinergic agents, scopolamine alone and scopolamine pretreatment and acetyl-L-carnitine (ALC) on visual event-related potentials (ERPs) in a monkey performing in a go/no-go visual oddball discrimination task. The same monkey was studied repeatedly for a period extending over 1.5 years. Scopolamine is known to cause cognitive impairment in primates. In the concentrations used, primary evoked potentials did not change significantly whereas P300 latency increased maximally 20-40 min following scopolamine administration. Acetyl-L-carnitine on its own increased P300 amplitude and decreased its latency. When ALC administration was preceded by scopolamine, both P300 latency and amplitude maximally increased in 25-45 min. Apparently ALC's effect on the latency and amplitude of visual P300 of the monkey is largely via muscarinic mechanisms. Our results suggest that scopolamine may provide a valuable tool to separate cognitive from primary visual processes.

Acetylcarnitine↗
PubMed1990

Effects of concurrent manipulations of nicotinic and muscarinic receptors on spatial and passive avoidance learning.

The present study investigates the effects of concurrent manipulations of nicotinic and muscarinic cholinergic receptors on spatial and passive avoidance learning/retention in rats. Daily pretraining test injections of combinations of the subthreshold doses of muscarinic (scopolamine 0.3 mg/kg) and nicotinic (mecamylamine 2.5 mg/kg or 10 mg/kg) antagonists impaired acquisition of the water-maze task (WM). Drug-induced deficits were also observed during the retention trial: the groups injected with scopolamine 0.3 mg/kg, mecamylamine 10 mg/kg and scopolamine 0.3 mg/kg in combination with mecamylamine 2.5 mg/kg showed reduced spatial bias compared with controls. Single preretention test injections of the combination of subthreshold doses of mecamylamine (10 mg/kg) and scopolamine (0.8 mg/kg) impaired memory retrieval in WM. Combined pretraining injections of subthreshold doses of scopolamine (1.0 mg/kg) and mecamylamine (10 mg/kg) induced a severe passive avoidance impairment comparable to 2.0 mg/kg of scopolamine. However, preretention test injections did not impair passive avoidance retention. Either single or combined injections of hexamethonium (5.0 mg/kg, SC) and methylscopolamine (1.0 mg/kg) did not impair either passive avoidance or water-maze performance. The present results suggest that 1) nicotinic and muscarinic systems jointly modulate performance in spatial and avoidance learning tasks and 2) cholinergic antagonists affect acquisition functions more effectively than retention ability. These findings may be relevant to the clinical disorders, like Alzheimer's disease, which are associated with a loss of both cholinergic neurons and nicotinic receptors.

Animals↗
PubMed1991

The behavioral effects of heptyl physostigmine, a new cholinesterase inhibitor, in tests of long-term and working memory in rodents.

We assessed the effects of heptyl physostigmine, a new cholinesterase inhibitor, in a mouse tail-flick (TF) test, a mouse and rat passive avoidance test, a rat conditioned suppression-of-drinking (CSD) test, a rat Random Interval (RI) response rate test and a rat delayed matching-to-position (DMTP) test. In the TF test, a dose of 8.0 mg/kg of heptyl induced a significant antinociceptive effect that was in excess of 75% of the maximum possible effect 300 minutes after administration. In the mouse passive avoidance test, a dose of 3.0 mg/kg of heptyl fully reversed, and a dose of 1.0 mg/kg partially reversed, a scopolamine-induced (0.2 mg/kg) deficit. In the rat passive avoidance test, a dose of 8.0 mg/kg fully reversed a scopolamine-induced (0.2 mg/kg) deficit, while a dose of 4.0 mg/kg of heptyl was without effect. In the same experiment, a dose of 0.6 mg/kg of physostigmine partially reversed the scopolamine-induced deficit. In the CSD test, a dose of 8.0 mg/kg of heptyl fully reversed, and doses of 1.0 and 4.0 mg/kg of heptyl partially reversed, the deficit induced by scopolamine (0.4 mg/kg). In the RI response rate test, doses of 8.0 mg/kg and 0.6 mg/kg of physostigmine fully suppressed lever pressing for food rewards. Doses of 4.0 mg/kg of heptyl and below had no effect on lever-pressing rates. In the working memory test (DMTP), 4.0 mg/kg heptyl partially reversed the scopolamine-induced deficit (0.2 mg/kg) in the number of correct choices made, but did not affect the scopolamine-induced deficit in the number of trials completed.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1996

Transient impairment of cholinergic function in the rat insular cortex disrupts the encoding of taste in conditioned taste aversion.

The muscarinic antagonist scopolamine blocks conditioned taste aversion (CTA) when microinjected bilaterally into the rat insular cortex shortly before the exposure of the rat to a novel taste (the conditioned stimulus, CS) in CTA training. Scopolamine has no effect when microinjected shortly after the exposure to the novel taste or shortly before the application of the malaise-inducing agent (unconditioned stimulus, UCS). Scopolamine does not affect sensory, motor and retrieval mechanisms required for performing the CTA task, and does not block CTA when injected into another cortical area. The effect of scopolamine is independent of the taste used as CS. Furthermore, microinjection of scopolamine into the insular cortex shortly before the pre-exposure to a new taste in a latent inhibition paradigm, impairs the attenuation of CTA by that pre-exposure. Other muscarinic antagonists, pirenzepine and AF DX-116, have an effect similar to that of scopolamine. Comparison of the dose-dependency curves of the muscarinic antagonists suggests a predominant role in CTA for M2 subtype receptors. Carbachol, a muscarinic agonist, also impairs the encoding of taste in the insular cortex, but the results are confounded by the ability of that ligand to induce seizures. Our findings suggest that cholinergic neuromodulation participates in processing the CS in the gustatory cortex in CTA, either by encoding novelty at the cellular level, or by instructing the neural circuits to store the novel taste representation.

Animals↗