Rigidity In Rats Research Articles

Study of the protective effect of fortified wheat grass with cow urine in experimentally induced parkinsonism

Parkinson’s disease (PD) is neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta which innervates the dorsal striatum. Since the existing anti Parkinson’s drugs encountered many side effects and need for prolonged treatment including questionable efficacy in the treatment, may cause Parkinson related movement problems, hallucinations and orthostatic hypotension. These reasons force the area of research to find improved treatments which will counteract the side effects and the draw backs of the existing treatment. Herbal drugs having diversified uses are always an alternative option to the synthetic drugs which are well known for their side and adverse effects . Using haloperidol induced catalepsy and muscle rigidity in rats the effects of Fortified Wheat grass (FWG) were studied. Haloperidol was administered at a dose of 1mg/kg; Fortified wheat grass with cow urine was administered at doses 150mg/kg & 300mg/kg. In conclusion fortified wheat grass with cow urine at doses of 150 and 300 mg/kg exhibited significant anti cataleptic activity, significantly reversed the haloperidol inhibited locomotor activity, restored the changes in behavioral assessment like akinesia, immobility in haloperidol administered rats, reduced the haloperidol induced rigidity. The possibility of pharmacological interactions between haloperidol and fortified wheat grass with cow urine should be further investigated in my research work.

Conversion from external fixator to intramedullary nail causes a second hit and impairs fracture healing in a severe trauma model

In poly-traumatic patients, second hits are known to potentiate the posttraumatic systemic inflammatory response, thus increasing the risk of multi-organ dysfunction. In accordance with "damage control orthopaedic surgery" principles, fractures are initially treated with external fixators, which are replaced by internal osteosynthesis once the immunological status of the patient is considered stable. Recently, we demonstrated that a severe trauma impaired the healing of fractures stabilized by external fixation during the entire healing period. The question arose, whether switching to intramedullary nailing increases the inflammatory response in terms of a second hit, leading to a further impairment of bone healing. Wistar rats received a femoral osteotomy stabilized by an external fixator. Simultaneously half of the rats underwent an additional thoracic trauma. After 4 days, the external fixator was replaced by an intramedullary nail in half of the rats of the two groups. The inflammatory response was evaluated by measuring serum C5a levels. Fracture healing was determined by three-point-bending, µCT, and histomorphometry. The thoracic trauma significantly increased C5a concentrations 6, 24, and 72 h after the second surgical intervention. After 40 days, conversion to intramedullary nailing considerably decreased the flexural rigidity of the callus, with no significant differences between rats with or without thoracic trauma. After 47 days, flexural rigidity in rats subjected to conversion remained decreased compared to animals solely treated by external fixation, particularly in combination with blunt chest trauma. The results indicate that accumulation of second hits after multiple injuries could lead to aggravation of the fracture healing outcome.

Assessment of axial bone rigidity in rats with metabolic diseases using CT-based structural rigidity analysis

Objectives This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone. Methods A total of 30 rats were divided equally into normal, ovariectomized, and partially nephrectomized groups. Cortical and trabecular bone segments from each animal underwent micro-CT to assess their average and minimum axial rigidities using structural rigidity analysis. Following imaging, all specimens were subjected to uniaxial compression and assessment of mechanically-derived axial rigidity. Results The average structural rigidity-based axial rigidity was well correlated with the average mechanically-derived axial rigidity results (R2 = 0.74). This correlation improved significantly (p < 0.0001) when the CT-based Structural Rigidity Analysis (CTRA) minimum axial rigidity was correlated to the mechanically-derived minimum axial rigidity results (R2 = 0.84). Tests of slopes in the mixed model regression analysis indicated a significantly steeper slope for the average axial rigidity compared with the minimum axial rigidity (p = 0.028) and a significant difference in the intercepts (p = 0.022). The CTRA average and minimum axial rigidities were correlated with the mechanically-derived average and minimum axial rigidities using paired t-test analysis (p = 0.37 and p = 0.18, respectively). Conclusions In summary, the results of this study suggest that structural rigidity analysis of micro-CT data can be used to accurately and quantitatively measure the axial rigidity of bones with metabolic pathologies in an experimental rat model. It appears that minimum axial rigidity is a better model for measuring bone rigidity than average axial rigidity.

Assessment of axial bone rigidity in rats with metabolic diseases using CT-based structural rigidity analysis

ObjectivesThis study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.MethodsA total of 30 rats were divided equally into normal, ovariectomized, and partially nephrectomized groups. Cortical and trabecular bone segments from each animal underwent micro-CT to assess their average and minimum axial rigidities using structural rigidity analysis. Following imaging, all specimens were subjected to uniaxial compression and assessment of mechanically-derived axial rigidity.ResultsThe average structural rigidity-based axial rigidity was well correlated with the average mechanically-derived axial rigidity results (R2 = 0.74). This correlation improved significantly (p < 0.0001) when the CT-based Structural Rigidity Analysis (CTRA) minimum axial rigidity was correlated to the mechanically-derived minimum axial rigidity results (R2 = 0.84). Tests of slopes in the mixed model regression analysis indicated a significantly steeper slope for the average axial rigidity compared with the minimum axial rigidity (p = 0.028) and a significant difference in the intercepts (p = 0.022). The CTRA average and minimum axial rigidities were correlated with the mechanically-derived average and minimum axial rigidities using paired t-test analysis (p = 0.37 and p = 0.18, respectively).ConclusionsIn summary, the results of this study suggest that structural rigidity analysis of micro-CT data can be used to accurately and quantitatively measure the axial rigidity of bones with metabolic pathologies in an experimental rat model. It appears that minimum axial rigidity is a better model for measuring bone rigidity than average axial rigidity.

Muscle relaxant and neurotoxic activities of intrathecal baclofen in rats

Intrathecal baclofen therapy by the continuous intrathecal infusion of baclofen has been shown to be an effective treatment for spasticity in patients with spinal cord injury, cerebral palsy, traumatic brain injury, multiple sclerosis and other disorders. To demonstrate the efficacy and safety of intrathecal baclofen therapy, we investigated the muscle relaxant and neurotoxic activities of intrathecal baclofen in rats, compared with intravenous baclofen. Intrathecal and intravenous administration of baclofen dose-dependently inhibited the anemic decerebrate rigidity with ED 50 values of 0.31 μg/animal (=1.1–1.3 μg/kg) and 0.43 mg/kg, respectively. Intrathecal administration of baclofen induced no noticeable changes in a spontaneous electroencephalogram at 30 μg/animal. Intravenous administration of baclofen induced an abnormal electroencephalogram with flat waves in all the animals and the no-observed-effect level was estimated to be 5 mg/kg. In some animals, intravenous administration of baclofen induced sporadic spikes or sharp waves with background flat waves, indicating inhibitory and excitatory effects on the central nervous system. In conclusion, intrathecal administration of baclofen dose-dependently inhibited anemic decerebrate rigidity in rats and the effective dose was more than 300 times lower than that of intravenous baclofen. The safety margin of intrathecal baclofen was greater than that of intravenous baclofen (≥97 versus 12). These results suggest that intrathecal baclofen therapy is superior to systemic baclofen therapy in both efficacy and safety.

Development of GABA-sensitive spasticity and rigidity in rats after transient spinal cord ischemia: A qualitative and quantitative electrophysiological and histopathological study

Transient spinal cord ischemia may lead to a progressive degeneration of spinal interneurons and subsequently to increased hind limb motor tone. In the present work we sought to characterize the rigidity and spasticity components of this altered motor function by: i) tonic electromyographic activity measured in gastrocnemius muscle before and after ischemia, ii) measurement of muscle resistance during the period of ankle flexion and corresponding changes in electromyographic activity, iii) changes in Hoffmann reflex, and, iv) motor evoked potentials. In addition the effect of intrathecal treatment with baclofen (GABA B receptor agonist; 1 μg), nipecotic acid (GABA uptake inhibitor; 300 μg) and dorsal L2–L5 rhizotomy on spasticity and rigidity was studied. Finally, the changes in spinal choline acetyltransferase (ChAT) and vesicular glutamate transporter 2 and 1 (VGLUT2 and VGLUT1) expression were characterized using immunofluorescence and confocal microscopy. At 3–7 days after ischemia an increase in tonic electromyographic activity with a variable degree of rigidity was seen. In animals with modest rigidity a velocity-dependent increase in muscle resistance and corresponding appearance in electromyographic activity (consistent with the presence of spasticity) was measured during ankle rotation (4–612°/s rotation). Measurement of the H-reflex revealed a significant increase in Hmax/Mmax ratio and a significant loss of rate-dependent inhibition. In the same animals a potent increase in motor evoked potential amplitudes was measured and this change correlated positively with the increased H-reflex responses. Spasticity and rigidity were consistently present for a minimum of 3 months after ischemia. Intrathecal treatment with baclofen (GABA B receptor agonist) and nipecotic acid (GABA uptake inhibitor) provided a significant suppression of spasticity, rigidity, H-reflex or motor evoked potentials. Dorsal L2–L5 rhizotomy significantly decreased muscle resistance but had no effect on increased amplitudes of motor evoked potentials. Confocal analysis of spinal cord sections at 8 weeks–12 months after ischemia revealed a continuing presence of ChAT positive α-motoneurons, Ia afferents and VGLUT2 and VGLUT1-positive terminals but a selective loss of small presumably inhibitory interneurons between laminae V–VII. These data demonstrate that brief transient spinal cord ischemia in rat leads to a consistent development of spasticity and rigidity. The lack of significant suppressive effect of dorsal L2–L5 rhizotomy on motor evoked potentials response indicates that descending motor input into α-motoneurons is independent on Ia afferent couplings and can independently contribute to increased α-motoneuronal excitability. The pharmacology of this effect emphasizes the potent role of GABAergic type B receptors in regulating both the spasticity and rigidity.

Chronic administration of rotenone increases levels of nitric oxide and lipid peroxidation products in rat brain

The complex I inhibitor rotenone is a neurotoxin that has been proposed to induce Parkinson-like degeneration. As the mechanisms of rotenone toxicity are not fully understood, the present study addresses the question of whether rotenone induces NO production and lipid peroxidation-like products, that is, thiobarbituric acid reactive substances (TBARS). Rotenone at a dose of 1.5 mg kg −1 ip was administered to rats daily for 10, 20, 30, and 60 days, and NO and TBARS were measured in the frontal cortex and in the striatum. On the 1st and 10th day, there were no increases in NO and TBARS levels, after 20 days, the NO and TBARS levels were increased in the striatum. After 30 and 60 days, NO and TBARS levels were increased in striatum and frontal cortex. Behaviorally, on days 30 and 60, the rats exhibited akinesia and rigidity in the catalepsy test. These results show that chronic administration of rotenone over a long period is capable of increasing NO and TBARS in the cortex and striatum and mimics Parkinson's disease (PD)-like behavioral symptoms that are akinesia and rigidity in rats.

Contribution of the serotonin 5-HT 1A receptor agonism of 8-OH-DPAT and EMD 128130 to the regulation of haloperidol-induced muscle rigidity in rats

The aim of the present study was to find out whether (±)-8-hydroxy-2(di- n-propylamino)tetralin (8-OH-DPAT), a prototypical 5-HT 1A agonist, and ( R)-(−)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane HCl (EMD 128130), a compound with serotonin 5-HT 1A-agonist and dopamine D 2-like antagonist properties, are able to attenuate the haloperidol-induced (1 mg/kg) muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic (EMG) method that simultaneously measured the mechanical muscle resistance (MMG) of the rat’s hind foot to passive movements in the ankle joint, and the EMG activity of two antagonist muscles. Both 8-OH-DPAT (0.125–0.5 mg/kg i.p.) and EMD 128130 (1–10 mg/kg i.p.) dose-dependently decreased the haloperidol-enhanced MMG to passive movements, as well as the tonic and the long-latency reflex EMG activities. Provided these results can be extrapolated to humans, the efficacy of EMD 128130 in relieving the haloperidol-induced muscle rigidity supports the concept that novel antipsychotics with 5-HT 1A agonist and dopamine D 2 antagonist activities should have a favourable extrapyramidal side-effect profile.

Discrimination of morphine- and haloperidol-induced muscular rigidity and akinesia/catalepsy in simple tests in rats

The present study was conducted to establish a simple method for measuring muscular rigidity in rats, which could be used for screening and is able to discriminate between rigidity and akinesia/catalepsy. Therefore, we treated rats with morphine (30 mg/kg i.p.), since large doses of morphine lead to muscular rigidity and akinesia. We measured muscular rigidity with a new method by determining the resistance of the hindlimb to passive flexion in the ‘balance test’ and also checked haloperidol (3 mg/kg i.p.) treated rats for muscular rigidity. Furthermore, catalepsy was also tested after administration of each of these drugs. Then, the influence of D 1-like and D 2-like dopamine receptor stimulation on muscular rigidity and catalepsy was studied. Therefore, the partial D 1 agonist SKF 38393 (3 and 8 mg/kg s.c.), the D 2/ D 1 agonist pergolide (0.25 and 0.5 mg/kg i.p.) and the dopamine precursor l-DOPA (50 and 100 mg/kg i.p.) were administered up to 30 min before muscular rigidity was measured in morphine-treated rats. The results showed that morphine, but not haloperidol led to muscular rigidity, whereas both drugs led to positive scores in the catalepsy test. The dopaminergic drugs partly antagonized the morphine-induced muscular rigidity in the doses applied, but not the catalepsy. Apparently, rigidity, akinesia/catalepsy produced by morphine can be discriminated from that produced by haloperidol in simple and quick tests.

( S)-4C3HPG, a mixed group I mGlu receptor antagonist and a group II agonist, administered intrastriatally, counteracts parkinsonian-like muscle rigidity in rats

The aim of the present study was to determine whether S-4-carboxy-3-hydroxyphenylglycine ( S)-4C3HPG, a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, attenuated parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano and electromyographic method, which measured simultaneously the muscle resistance (MMG) of the rat’s hind foot to passive extension and flexion in the ankle joint and the electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). ( S)-4C3HPG injected in doses of 5 and 15 μg/0.5 μl bilaterally, into the rostral region of the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and the enhanced electromyographic activity (EMG). The present results suggest that blockade of mGluR1 receptors and/or activation of mGluR2 ones, localized in the rostral part of the striatum, may be responsible for the anti-parkinsonian effect of ( S)-4C3HPG.

SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats.

The aim of the present study was to find out whether blockade of adenosine A(2A) receptors by a selective antagonist, SCH 58261, influenced parkinsonian-like muscle rigidity. Muscle tone was examined using a combined mechano- and electromyographic method which simultaneously measured muscle resistance (MMG) of a rat hindfoot to passive extension and flexion in the ankle joint and electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity produced by reserpine (5 mg/kg + alpha-methyl-p-tyrosine, 250 mg/kg) was antagonized by SCH 58261 (0.1-5 mg/kg). SCH 58261 (5 mg/kg) also reduced reserpine-enhanced tonic and reflex EMG activities in both the gastrocnemius and the tibialis muscles. Moreover, SCH 58261 in doses of 1 and 5 mg/kg abolished muscle resistance induced by haloperidol (0.5 mg/kg). However, only the highest dose of SCH 58261 (5 mg/kg) decreased tonic EMG activity enhanced by haloperidol. Administration of L-DOPA (75 and 100 mg/kg) dose-dependently decreased the muscle resistance as well as tonic EMG activity evoked by haloperidol. Combined administration of SCH 58261 (0.1 mg/kg) and L-DOPA (50 mg/kg) in doses which did not affect the haloperidol-induced muscle rigidity produced a pronounced synergistic effect. The ability of SCH 58261 to diminish the parkinsonian-like muscle rigidity and to potentiate the effect of L-DOPA in this model seems to indicate a therapeutic value of this compound in the treatment of Parkinson's disease.

Efficacy of pramipexole, a new dopamine receptor agonist, to relieve the parkinsonian-like muscle rigidity in rats

The aim of the present study was to assess the efficacy of pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochloride), a new dopamine D 2/D 3 receptor agonist, to attenuate parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic (EMG) method, which simultaneously measured the muscle resistance of a rat's hindlimb to passive extension and flexion at the ankle joint, and the EMG acitivity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg) injected in combination with α-methyl-p-tyrosine (250 mg/kg) or by haloperidol (0.5 mg/kg). Pramipexole in doses of 0.5–5 mg/kg antagonized both reserpine+α-methyl- p-tyrosine- and haloperidol-induced muscle rigidity. Pramipexole also reduced reserpine-enhanced tonic and reflex EMG activities in the gastrocnemius muscle. The present results suggest that stimulation of the postsynaptic dopamine receptor may be chiefly responsible for the antiparkinsonian action of pramipexole. The ability of pramipexole to diminish the parkinsonian-like muscle rigidity seems to indicate a therapeutic value of this compound in the treatment of Parkinson's disease.

L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats.

It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology of Parkinson's disease. Therefore, a search for new compounds which block glutamatergic receptors and show antiparkinsonian properties in animal models of this disease seems to be justified. The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like muscle rigidity and catalepsy induced by haloperidol in rats. The muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic (EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior muscles. L-701,324 (2.5-40 mg/kg IP) dose-dependently decreased the muscle tone enhanced by haloperidol (1-5 mg/kg IP). Likewise, the haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost abolished by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5 mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25-5 mg/kg IP) given alone or together with haloperidol (0.5-1 mg/kg IP) disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed balance and loss of control over their hind limbs. The present study suggests that L-701,324 exhibits a beneficial action in the animal model of parkinsonian rigidity, but not that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects.

The role of striatal glutamate receptors in models of Parkinson's disease.

The aim of the study was to examine the effect of antagonists of the NMDA receptor on the parkinsonian-like muscle rigidity in rats. Reserpine and haloperidol increased the muscle resistance of the hind foot to passive movements, as well as the reflex electromyographic (EMG) activity in the gastroenemius and tibialis anterior muscles. MK-801 (0.32-1.28 mg/kg s.c.), an uncompetitive antagonist of the NMDA receptor, and L-701,324 (5-40 mg/kg i.p.), an antagonist of the glycine site, reduced the muscle tone and the reflex EMG activity enhanced by reserpine or haloperidol. AP-5 (2 and 5 micrograms/0.5 microliter), a competitive antagonist of the NMDA receptor, and 5,7-dichlorokynurenic acid (1.0-4.5 micrograms/0.5 microliter), the glycine site antagonist injected bilaterally into the rostral striatum, inhibited the muscle rigidity induced by haloperidol. In contrast, AP-5, injected alone bilaterally into the intermediate-caudal striatum induced muscle rigidity. The present results suggest that: (1) the inhibitory effect of the NMDA receptor antagonists on the parkinsonian-like muscle rigidity depends, at least partly, on their action on the rostral striatum; (2) the blockade of NMDA receptors in the intermediate-caudal striatum may reduce the beneficial impact of these compounds.

Involvement of spinal adenosine A 1 and A 2 receptors in fentanyl-induced muscular rigidity in the rat

In the present study, using hydrophilic adenosine antagonists either selective to A 1 or A 2 receptors, we investigated the central and spinal adenosinergic participation in fentanyl-induced muscular rigidity. Adult Sprague–Dawley rats were anesthetized with ketamine and were under mechanical ventilation. Fentanyl (100 μg/kg, i.v.) consistently elicited electromyographic (EMG) activation in the sacrococcygeal dorsalis lateralis muscle. This implied muscular rigidity was not blocked by i.c.v. administration of the adenosine A 1 antagonist, 1-allyl-3,7-dimethyl-8- p-sulfophenyl-xanthine (ADSPX; 20 or 40 nmol/2.5 μl), except at higher dose (80 nmol). Equimolar doses of the adenosine A 2 antagonist, 3,7-dimethyl-1-propargylxanthane (DMPX), did not exert any inhibitory effect on fentanyl-induced rigidity. Intrathecal (i.t.) administration of the same doses of ADSPX (20, 40 or 80 nmol/10 μl) appreciably suppressed the EMG activation. However, the rigidity was only inhibited by 40 or 80 nmol (i.t.) of DMPX, but not by the lowest dose. High-dose (80 nmol, i.t.) adenosine A 1 or A 2 antagonist per se did not induce motor impairment or hindlimb paralysis in conscious animals. These results suggest that adenosine A 1 and A 2 receptors in the spinal cord may play a more crucial role than those in the central nervous system (CNS) in fentanyl-induced muscular rigidity in rats.

Power spectral analysis of electromyographic and systemic arterial pressure signals during fentanyl-induced muscular rigidity in the rat

We have measured electromyographic (EMG) and systemic arterial pressure (SAP) signals during fentanyl-induced muscular rigidity in adult male Sprague-Dawley rats anaesthetized initially with ketamine 120 mg kg-1 i.p. during controlled ventilation. Fentanyl 100 micrograms kg-1 i.v. induced significant increase in EMG activity, recorded from the sacrococcygeus dorsi lateralis muscle. Power spectral analysis revealed that this was produced by an increase in the root mean square and a decrease in the mean power frequency values of the signals, signifying recruitment and synchronous activation of motor units. Together with transient hypotension and bradycardia, power spectral analysis of the SAP signals demonstrated a reduced but maintained power density of the frequency components that represent respiratory, baroreceptor and vasomotor activities. All these effects were only demonstrated unequivocally in rats maintained by i.v. infusion of ketamine until 10 min before the administration of fentanyl. We conclude that analysis of the temporal alterations in the spectral components of the EMG and SAP signals in rats during mechanical ventilation provides a sensitive method of measuring fentanyl-induced muscular rigidity and the accompanying alterations in haemodynamic variables.

Automated method for the measurement of fentanyl-induced muscular rigidity

An automated method is described that can accurately and reliably measure weight displacement resulting from hindlimb extension due to muscular rigidity following opioid administration in rats. IV administration of fentanyl (0.035 mg/kg) immediately induced rigidity. Rigidity was dose dependently reversed by the α 2-agonist clonidine with an ED 50 value equal to 0.011 mg/kg IV. Second, rigidity was restored following administration of the α 2-antagonist idazoxan (0.3 mg/kg, IV) thereby confirming an α 2-mediated mechanism of action. Previously, reversal of fentanyl-induced muscular rigidity was measured by subjective rating criteria not suitable for quantitative potency comparisons. The new automated rigidity model provides a simple yet precise measurement of the ability of α 2-agonist to attenuate opioid-induced muscular rigidity in rats.

Cortical representation of components of the gastroduodenal complex and role of the vagus nerves in regulation of visceral afferentation

Bilateral microinjection of delta-sleep-inducing peptide (DSIP) (10.0 nmol) into the substantia nigra provoked hypokinesia and rigidity in rats observed during 4.0 hours. Injection of DSIP in dose of 5.0 nmol into the substantia nigra or into the nuclei caudati in dose of 10.0 nmol did not induce such symptoms. The enhanced slow-wave activity was recorded in caudate nuclei during hypokinesia and rigidity which demonstrated the formation of the generator of pathologically enhanced excitation (GPEE). The systemically cyclodol administration resulted in abolishment of rigidity and increase in locomotor activity. The conclusion is that bilateral intranigral DSIP injection caused acute parkinson syndrome in rats due to the formation of cholinergic GPEE in caudate nuclei. The hyperactive caudate nuclei act as the pathologic determinant which induces the parkinson syndrome.

Involvement of coerulospinal noradrenergic pathway in fentanyl-induced muscular rigidity in rats

Unilateral, site-specific microinjection of fentanyl ( 2.5 μ g 50 nl ) into the locus coeruleus (LC) in Sprague-Dawley rats anesthetized with ketamine evoked a significant increase in the electromyographic activity recorded from both caudal lateral extensor and gastrocnemius muscles. This correlate of opiate-induced muscular rigidity was appreciably antagonized by a pretreatment with the specific α 1-adrenoceptor blocker, prazosin (250 μg/kg, i.v.). On the other hand, an equimolar dose (0.65 μmol/kg) of the specific α 2-adrenoceptor blocker, yohimbine (0.23 mg/kg, i.v.) failed to prevent the occurrence of fentanyl-induced EMG activation. We suggest that the coerulospinal noradrenergic pathway may be directly involved in the elicitation of muscular rigidity by fentanyl, possibly via α 1-adrenoceptors in the spinal cord.

Differential effects of prazosin and yohimbine on fentanyl-induced muscular rigidity in rats

Whereas muscular rigidity is a well-known phenomenon that is related to anesthesia induced by large doses of narcotic drugs, the precise underlying mechanism(s) remain to be fully elucidated. This study investigated the possible role of noradrenergic neurotransmission and the participation of α-adrenoceptors in this phenomenon. Male Sprague-Dawley rats, under ketamine-induced anesthesia (120 mg/kg, i.p.) and with proper control of respiration, body temperature and end-tidal CO 2 were used. Intravenous administration of fentanyl (lOO g/kg) consistently caused a significant increase in the electromyographic (EMG) activity, recorded from both gastrocnemius and abdominal reetus muscles. This implied muscular rigidity was markedly antagonized by pretreatment with the specific α 1-adrenoceptor blocker, prazosin (50 or 250μg/kg, i.V.). This antagonism occurred in spite of a high level of fentanyl in the plasma, as determined by radioimmunoassay. The specific α 2-adrenoceptor blocker, yohimbine (1.15 or 2.3 mg/kg, i.V.), on the other hand, not only failed to prevent fentanyl-induced activation of the EMG, but actually potentiated the response. It is concluded that noradrenergic neurotransmission, possibly originating from the locus coeruleus, may participate in the elicitation of muscular rigidity by fentanyl. Furthermore, this process may involve an excitatory action through α 1-, and an inhibitory action through α 2-adrenoceptors, in the spinal cord.