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PubMed1997

Apoptosis in the rat penis after penile denervation.

PURPOSE: Despite the advances in nerve sparing prostatectomy for prostate cancer, some patients develop impotence or subjectively complain of a decrease in penile size. We hypothesized that these clinical observations may be explained by injury to the cavernous nerves resulting in programmed cell death (apoptosis) within the penis. We utilized a rat model of penile denervation in order to demonstrate apoptosis after denervation. METHODS AND MATERIALS: Fifteen male Sprague Dawley rats underwent abdominal exploration and bilateral cavernous neurotomy. Fifteen sham operations were performed as normal controls. The rats were sacrificed on postoperative day 1,2,3,6, and 10 and their penises were harvested. Messenger RNA was extracted and probed on a northern blot for sulfated glycoprotein-2 (SGP-2). SGP-2 is a gene product reported to be elevated in apoptotic tissues. Separate denervated and sham rats were used for DNA extraction (sacrificed postoperative day #2) in order to demonstrate the internucleosomal DNA fragmentation (laddering) found in apoptotic tissues. In addition, in situ histology was performed with ISEL techniques (in situ end labeling) to stain for apoptotic nuclei in denervated rats. RESULTS: Northern blot analysis showed a large increase in SGP-2 mRNA expression in the denervated rats with little detected in the sham operated group. DNA extraction studies revealed the presence of internucleosomal DNA fragmentation on agarose gel (a marker for apoptosis) in the denervated group versus intact high molecular weight DNA in the sham rats. In addition, in situ staining of denervated penile erectile tissue demonstrated apoptotic nuclei in the cavernous tissue. CONCLUSION: Apoptosis of penile erectile tissue occurs after denervation of the rat penis. This has not been previously described in the literature and may offer some explanation at the molecular level concerning the mechanism of impotence and/or decrease in penile size after radical prostatectomy.

Animals↗
PubMed1976

The role of acetylcholine receptors and acetylcholinesterase activity in the development of denervation supersensitivity.

Strips of muscle from innervated and denervated rat hemidiaphragm were tested for sensitivity to acetylcholine and to carbachol. For both agonists, denervation (6-8 days) produced notable supersensitivity. However, the increase in sensitivity to acetylcholine (ca. 600-fold) was much greater than that to carbachol (ca. 51-fold). Denervation also produced an increase in [3H]alpha-bungarotoxin binding (ca. 20-fold), presumably indicative of an increase in the number of acetylcholine receptors. In addition to causing increases in tissue sensitivity and receptor number, denervation caused a marked loss of acetylcholinesterase activity (ca. 70%) and a modest loss of butyrylcholinesterase activity (ca. 20%). When innervated muscle was pretreated with eserine (5 X 10(-5) M), there was a loss of acetylcholinesterase activity (ca. 86%) and butyrylcholinesterase activity (ca. 36%). Simultaneously, there was an increase in tissue sensitivity to acetylcholine (ca. 26-fold). When denervated muscle was pretreated with eserine, there was no loss of enzyme activity beyond that caused by denervation. Furthermore, eserine pretreatment did not increase denervated muscle sensitivity to acetylcholine. The data suggest that both an increase in acetylcholine receptors and a decrease in acetylcholinesterase activity contribute to the phenomenon of denervation supersensitivity.

Acetylcholine↗
PubMedDate not supplied

Effects of chemical denervation with 6-hydroxydopamine on myocardial responsiveness to isoproterenol in rabbits.

This study examined the hypothesis that chemical denervation with 6-hydroxydopamine (6-OHDA) would increase myocardial responsiveness to isoproterenol. Five days previously, 15 New Zealand white rabbits were given 60 mg/kg 6-OHDA intravenously. Fifteen control rabbits received vehicle. Hemodynamic, coronary blood flow (CBF), and cardiac output measurements were obtained before and during isoproterenol infusion (0.5 microgram/kg/min for 15 min). Norepinephrine tissue content, beta-adrenoceptor number (Bmax) and affinity (Kd), cyclic AMP content and cyclic AMP-phosphodiesterase (PDE) activity were measured in the subepicardium (EPI) and subendocardium (ENDO). Myocardial norepinephrine content was significantly decreased from 1263 +/- 292 (EPI) and 874 +/- 221 ng/g tissue (ENDO) in the control to 148 +/- 33 (EPI) and 90 +/- 45 ng/g tissue (ENDO) in the denervated group. There were no significant changes in cyclic AMP-PDE activity or Bmax and Kd of beta-adrenoceptors. Cyclic AMP content was similar at baseline, but controls had a significantly larger increase (123-155%) during isoproterenol infusion when compared to the denervated group (27-37%). The denervated animals showed a smaller increase in cardiac output during isoproterenol infusion (from 203 +/- 30 to 235 +/- 26 ml/min), when compared to the control animals (from 135 +/- 18 to 216 +/- 42 ml/min). Baseline CBF was significantly higher in the EPI but not ENDO of the denervated group (185 +/- 20 ml/100 g/min in EPI and 150 +/- 8 in ENDO) compared to the control group (108 +/- 13 in EPI and 133 +/- 17 in ENDO). The relative increase in CBF during isoproterenol infusion was smaller in the denervated group (44-45%) than the control group (107-109%). Isoproterenol infusions of 0.1 and 2.5 micrograms/kg/min showed similarly depressed coronary blood flow responses in denervated animals. Thus, the chemically denervated animals did not have beta-adrenoceptor upregulation, exhibited a lesser increase in cyclic AMP with isoproterenol, and had a reduced functional and coronary blood flow response to isoproterenol. This occurred without any significant change in beta-adrenoceptor number or affinity, or in cyclic AMP-phosphodiesterase activity, indicating there may be receptor uncoupling or other changes in the signal transduction pathway.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Evaluation of the role of sympathetic denervation on hepatic function.

It is acknowledged that autonomic nerves play an important role on liver function. Sympathetic nerve is the main component of them. This study is to evaluate the effects of sympathetic denervation of the liver on liver function in the normal and chemically injured liver, and its influence on liver regeneration. Eighty healthy male Wistar rats were divided randomly into four groups: Sham group, carbon tetrachloride group (CCL4), 6-hydroxydopamine group (6-OHDA), and CCL4+6-OHDA group. Chemical denervation model was made by injection of 6-OHDA (2ml, 100mg/l) through the mesenteric vein of jejunum loop. Acute liver injury model was established by using CCL4. Blood chemistry, ATP, arterial ketone body ratio (AKBR) and indocyanine green (ICG(15)) were measured in each group after administration of sympathetic denervation or/and acute liver injury. Liver regeneration was assessed with hepatic mass index (HMI), rate of liver regeneration (RLR), mitotic index (MI) and the rates of DNA synthesis under sympathetic denervation. Chemical denervation resulted in significant changes of liver function tests under acute liver injury, and had beneficial effects on protein anabolism, metabolism of bilirubin and energy, and ICG excretion, meanwhile, alleviated low potassium in serum. However, sympathetic denervation only had no effects on liver function tests. It decreased significantly in sympathetic denervation group for HMI, RLR, MI and the rate of DNA synthesis with 3H-TdR (P<0.01). It is concluded that sympathetic denervation can alleviate liver injury by CCL4, impair liver regeneration, but has no effects on liver function tests under normal.

Journal Article↗
PubMed1998

Metabolic alterations in the chronically denervated dog heart.

OBJECTIVE: Previous studies have shown that chronic cardiac denervation impairs myocardial glucose oxidation. To investigate this further we tested whether the tissue content of glucose transporters, activity of glycolytic enzymes or metabolic capacity of pyruvate dehydrogenase were altered. Moreover, we investigated whether the decline in glucose utilization was associated with an upregulation of proteins and enzymes involved in fatty acid handling. Chronic cardiac denervation results also in decreased left ventricular efficiency. We explored whether alterations in mitochondrial properties could be held responsible for this phenomenon. METHODS: Twelve adult dogs were included in the study. In 6 of them chronic cardiac denervation was accomplished by surgical ablation of the extrinsic nerve fibers. The other 6 dogs were sham-operated. Biopsies were obtained from the left ventricle after 4-5 weeks of denervation. The content or enzymatic activity of proteins involved in fatty acid and glucose handling was assessed. Features of glutamate oxidation were measured in freshly isolated mitochondria. RESULTS: The content or activity of a set of fatty acid handling proteins did not change during chronic cardiac denervation. In contrast GLUT1 content significantly increased in the chronically denervated left ventricle, while the active form of pyruvate dehydrogenase declined (p < 0.05). Glutamate oxidation characteristics in freshly isolated mitochondria were not affected by chronic denervation. CONCLUSION: The impairment of glucose oxidation in the chronically denervated myocardium is most likely caused by a decline of pyruvate dehydrogenase in its active form. It is unlikely that the decrease in work efficiency is caused by alterations in mitochondrial properties.

Animals↗
PubMed1998

Testicular denervation-induced nuclear changes in Leydig cell of hemicastrated adult rats.

In the adult male rat, hemicastration (HC) induces a remarkable enhancement of testosterone secretion from the Leydig cells of the remaining testis. We have observed previously that the denervation of inferior spermatic nerves inhibits this enhancement. The present experiments were designed to assess morphometrically whether or not this change had a cytological correlate in Leydig cells. At least five testes from each group (denervation plus HC, sham denervation plus HC and intact rats) were prepared for both optical and electron microscopy studies. The results showed that after 24 h of denervation, the nuclear volume of the Leydig cells in denervation plus HC rats was smaller (p < 0.01) than those of sham denervation plus HC (196.56 +/- 16.53 vs. 280.71 +/- 13.37), whereas both the volume density of heterochromatin (19.84 +/- 3.14 vs. 10.03 +/- 2.47%) and the heterochromatin index (expressed as periphery heterochromatin area divided by nuclear perimeter, 0.149 +/- 0.046 vs. 0.094 +/- 0.026) were significantly (p < 0.01) higher in denervation plus HC rats than in its sham groups. No changes in Leydig cell numbers or cytoplasmic organelles were detected. The results suggest that some nuclear and heterochromatin-associated cellular activity might be inhibited by testicular denervation in hemicastrated rats.

Animals↗
PubMed2002

Effects of sympathetic denervation on the hyaluronan content of the anterior segment in the normal and traumatized rabbit eye.

PURPOSE: To determine whether there is any involvement of sympathetic nerves in the regulation of ocular hyaluronan production in the normal and traumatized rabbit iris. METHODS: Unilateral sympathetic denervation was performed by removing the right superior cervical ganglion. Hyaluronan concentrations in the iris and aqueous were measured with a radiometric assay at various time intervals after denervation. Peripheral iridectomy was also performed in both denervated and non-denervated eyes. RESULTS: Hyaluronan concentrations in the iris tissue after denervation were observed to have increased after 1 day, reaching a peak of 129.6 +/- 5.7 microg/g wet weight at day 3. Two weeks later, hyaluronan concentrations had fallen back to normal levels. Ocular trauma with peripheral iridectomy in denervated eyes caused an increase of hyaluronan content of up to 253.5 +/- 30.5 microg/g wet weight, which was not significantly different from hyaluronan concentrations observed after the same trauma in non-denervated eyes. CONCLUSION: Cervical sympathetic denervation results in a moderate increase of the hyaluronan content in the rabbit iris and does not appear to influence the hyaluronan response of the iris to trauma.

Animals↗
PubMed2005

Differential gene expression profiling of short and long term denervated muscle.

Skeletal muscle function and viability are dependent upon intact innervation. Peripheral nerve injury and muscle denervation cause muscle atrophy. Time to re-innervation is one of the most important determinants of functional outcome. While short-term denervation can result in nearly fully reversible changes in muscle mass, prolonged denervation leads to irreversible muscle impairment from profound atrophy, myocyte death and fibrosis. We performed transcriptional profiling to identify genes that were altered in expression in short-term (1 month) and long-term (3 month) denervated muscle and validated the microarray data by RT-PCR and Western blotting. Genes controlling cell death, metabolism, proteolysis, stress responses and protein synthesis/translation were altered in expression in the denervated muscle. A differential pattern of expression of genes encoding cell cycle regulators and extracellular matrix components was identified that correlated with the development of irreversible post-denervation changes. Genes encoding mediators of protein degradation were differentially expressed between 1 and 3 month denervated muscle suggesting different signaling networks are recruited over time to induce and maintain muscle atrophy. Understanding of the timing and type of pathological processes that are triggered by denervation may allow the design of interventions that delay or protect muscle from loss of nerve function.

Animals↗
PubMed1993

Denervated skeletal muscle: MR imaging. Work in progress.

PURPOSE: To evaluate the change in signal intensity of skeletal muscles after denervation and to determine the clinical usefulness of magnetic resonance (MR) imaging in diagnosis of denervation. MATERIALS AND METHODS: Denervated skeletal muscles associated with various forms of peripheral neuropathy and spinal radiculopathy were studied with MR imaging in 17 patients. RESULTS: On T1-weighted images, signal intensity of denervated muscles was normal in 14 patients and high in three. On T2-weighted images, all denervated muscles showed high signal intensity on at least one MR image. High signal intensity in the denervated muscles on T2-weighted images was observed 15 or more days after onset of paralysis. In two patients, signal intensity of denervated muscles returned to normal after relief of paralysis. CONCLUSION: MR imaging is a noninvasive and accurate method for use in diagnosis of denervation and may ultimately eliminate the need for electromyography.

Adipose Tissue↗
PubMed2002

Is the chronically denervated kidney supersensitive to catecholamines?

One method for discerning the role of the renal sympathetic nerves in the regulation of renal function has been to chronically denervate one kidney. One concern with this approach is that increased renal responsiveness to plasma levels of norepinephrine may develop over time. This may reduce the apparent magnitude of the effect of the renal nerves or indeed completely mask their effect. In the present experiment, we used the rabbit unilateral denervated kidney model to examine the acute renal blood flow responses to phenylephrine to determine if there were differences between the responses in chronically denervated kidneys compared with either intact or acutely denervated kidneys. In addition, we examined the responses in rabbits that had been made hypertensive using a continuous infusion of ANG II for 7 wk. We found that chronic denervation did not result in increased renal responsiveness to phenylephrine compared with either the intact or acutely denervated kidney, suggesting that differences in renal function between renal nerve-intact and -denervated kidneys observed in previous studies are unlikely to be confounded by supersensitivity. These results suggest that the unilateral denervated kidney model is a valid model to study the role of the renal nerves in the regulation of renal function.

Angiotensin II↗
PubMed1988

Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application.

Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.

3-Iodobenzylguanidine↗
PubMed1992

Myocardial adrenergic denervation supersensitivity depends on a postreceptor mechanism not linked with increased cAMP production.

BACKGROUND: Two major hypotheses have been proposed to explain catecholamine supersensitivity after myocardial denervation, but neither sufficiently explains certain features of the phenomenon. In addition, a nonsurgical method for long-term myocardial adrenergic denervation is desirable but has not been accomplished or described with respect to catecholamine supersensitivity. METHODS AND RESULTS: We have accomplished chronic myocardial adrenergic denervation by using 6-hydroxydopamine (6-OHDA). Sixteen weeks after 6-OHDA administration to newborn pigs, we found substantial myocardial adrenergic denervation associated with beta-adrenergic receptor (beta AR) downregulation. Despite decreased beta AR number, the dose of isoproterenol yielding 50% maximal heart rate change (ED50) was decreased, and heart rates during exercise showed increased responsiveness despite decreased circulating catecholamines. Thus, stimulation of fewer receptors yielded an increased response, implying improved signal transduction efficiency. Competitive binding studies with isoproterenol showed an increased proportion of beta AR with high-affinity binding in myocardial membranes from 6-OHDA pigs, suggesting that interaction between beta AR and cardiac G, may contribute to improved signal transduction efficiency. However, measures of adenylyl cyclase activity indicated marked reduction in beta AR-dependent and G2-dependent cAMP production in myocardial membranes from denervated animals despite a normal amount of cardiac Gs and decreased Gi. CONCLUSIONS: We have demonstrated that substantial, long-term myocardial adrenergic denervation is possible using 6-OHDA. Denervation supersensitivity in this model does not depend on enhanced cAMP stimulation but rather depends on postreceptor elements in the beta AR-responsive pathway that may be independent of Gs-activated adenylyl cyclase activity. In this model of adrenergic denervation supersensitivity, beta-receptors, through Gs, may be linked to an alternative effector that drives heart rate responsiveness.

Adenylyl Cyclases↗
PubMed1991

Immediate expansion of receptive fields of neurons in area 3b of macaque monkeys after digit denervation.

The short-term effect of total or partial single-digit denervation on receptive fields (RFs) of neurons in somatosensory cortex (area 3b) was examined in five macaque monkeys. In two animals, after denervation by amputation, it was found that electrode positions that initially recorded neurons with RFs on the amputated digit had new RFs extending from the wound. Often the new fields were on adjacent digits. Neurons with initial RFs that were partially amputated, or in some cases close to but not on the amputated digit, showed considerable expansion of the remaining RF. In three monkeys local anesthesia was used to provide a temporary denervation. In these experiments electrodes were placed in equivalent positions in both cortices. The effect on cortex contralateral to the denervation was similar to that seen with amputation. However, after anesthesia returned to the digit, the expanded RFs contracted. In cortex ipsilateral to the denervation, RFs were on the opposite unaffected hand. These also rapidly expanded and then contracted, with the same time course as their counterparts in cortex contralateral to the denervation. Because of the rapidity of the expansion and its temporary nature with short-term denervation, the basis of the effect is probably an unmasking of existing but normally unexpressed connections, which are normally inhibited by the intact output from the denervated area. The wide arborization fields of thalamocortical afferents provide a potential source for the unmasked sensitivity. A mechanism for the inhibition that normally suppresses the expression of large RFs is not readily apparent. However, work in other species suggests that peripheral C fibers provide the primary source of input to central inhibitory circuits.

Afferent Pathways↗
PubMed1999

Glycemic modulation of insulin/IGF-1 mediated skeletal muscle blood following sympathetic denervation in normal rats.

Both insulin and IGF-1 decrease vascular resistance and increase blood flow in skeletal muscle, and it has been suggested that the mechanistic action for insulin may be by increasing autonomic vasodilatory activity. In this study we evaluated the effects of insulin and IGF-1 on blood flow to denervated and non-denervated skeletal muscle as part of a continuing investigation into the mechanism of regulation of cardiovascular responses by these hormones. Normal rats were prepared for measurements of mean arterial pressure (MAP), heart rate (HR) and vascular flow in the left and right iliac artery. Resection of the left lumbar sympathetic chain increased flow (expressed as conductance, flow/MAP) in the denervated left iliac but not in the intact right artery. Subsequent insulin infusion where hypoglycemia was allowed to occur increased conductance in both arteries, but more so in the denervated artery. Similarly, IGF-1 infusion increased conductances in both intact and denervated iliac arteries, and the effect was slightly greater in the denervated artery. Insulin infusion when euglycemia was maintained increased conductance to a similar extent in denervated and intact iliac arteries. Contrastingly, IGF-1 infusion under euglycemic conditions resulted in a much greater increased conductance in the intact iliac. We conclude that both insulin and IGF-1 increase conductance directly and that glycemic status and sympathetic nerve activity modulate these responses. The insulin-induced increase in conductance in the denervated limb under hypoglycemic conditions suggest that hypoglycemic-stimulated epinephrine release may enhance the dilatory response. while the greater response to IGF-1 in the intact vessel under euglycemic conditions may be due to IGF-1 capacity to decrease sympathetic activity leading to an enhanced conductance.

Animals↗
PubMed1985

Pressor responsiveness in renal prehypertensive rabbits with a denervated kidney.

Norepinephrine was infused iv at several doses into four groups of conscious rabbits (six per group), and the pressor responses were recorded. The groups were 3-day sham-operated rabbits; 3-day, two-kidney rabbits with unilateral renal artery stenosis (RAS); 3-day, two-kidney rabbits with unilateral renal denervation; and 3-day, two-kidney rabbits with unilateral renal denervation plus RAS of the denervated kidney. The rabbits with RAS of an innervated kidney and those with RAS of a denervated kidney had the same pressor responses to norepinephrine, which were greater than the pressor responses in the sham-operated rabbits or in the rabbits with a denervated kidney but without RAS. Four additional groups of similarly prepared rabbits were infused with norepinephrine at 800 ng/min/kg body wt, and mean arterial pressure and cardiac output were determined before and during norepinephrine infusion. The rabbits with RAS of an innervated or of a denervated kidney had greater increases in total peripheral resistance as well as in mean arterial pressure during norepinephrine infusion than did the two groups of rabbits without RAS. This indicated that the rabbits with RAS also had increased vascular responses to norepinephrine. The concentration of norepinephrine in six denervated kidneys was extremely low as compared to that of six innervated kidneys. Because renal denervation did not diminish pressor and vascular hyperresponsiveness in 3-day RAS rabbits, the signal that originates in the kidney following RAS and that results ultimately in pressor and vascular hyperresponsiveness is not mediated by renal nerves.

Animals↗
PubMed1999

PET imaging of oxidative metabolism abnormalities in sympathetically denervated canine myocardium.

UNLABELLED: This study was designed to test the hypothesis that regional sympathetic denervation produces perfusion and metabolic alterations in myocardial tissue under resting conditions. METHODS: PET studies of myocardial sympathetic innervation, myocardial perfusion and oxygen utilization using [11C]hydroxyephedrine (HED), [13N]ammonia and 1-[11C]acetate, respectively, were performed before and approximately 2 and 8 wk after surgical left thoracotomy and regional chemical sympathetic denervation (n = 5). A second group of animals underwent the same surgical procedure but, so that they could serve as a sham control group, were not sympathetically denervated (n = 5). The second group of animals was imaged before and 2 wk after surgery. Images of the retention of [11C]HED taken from 50 to 60 min postinjection were used to differentiate sympathetically innervated and denervated regions of the left ventricle. Regions of interest were defined on polar plots of the [11C]HED retention, including the sympathetically denervated territory and normally innervated regions. Regions defined on the HED polar plots were then transferred to the [13N]ammonia and 1-[11C]acetate image data, and tracer kinetic models were fit to the regional time-activity curves to generate estimates of myocardial perfusion and oxidative metabolism. RESULTS: The average percentage of the left ventricle denervated in the group I animals was 13.1% +/- 7.3%. Significant reductions in oxidative metabolism were observed in the sympathectomized tissue both at 2 and 8 wk after surgery (22% and 15% reductions, respectively). Significant alterations in regional perfusion were not observed. No significant changes in oxidative metabolism or perfusion were observed in the sham control group. CONCLUSION: Regional sympathetic denervation alters oxidative metabolism but not perfusion in the denervated region of the heart.

Acetates↗
PubMed1985

Effects of chronic dietary lithium on behavioral indices of dopamine denervation supersensitivity in the rat.

The present study was designed to test the hypothesis that chronic lithium (Li) treatment could alter the behavioral manifestations of dopamine (DA) denervation supersensitivity. Rats were maintained on a Li diet continuously for 4 weeks before and 4 weeks after bilateral chemical denervation of DA terminal fields in the nucleus accumbens (N.Acc.) and the caudate nucleus (CN). We examined the behavioral responses of these animals to apomorphine (0.1 mg/kg s.c.) treatment 2 and 4 weeks postdenervation. Animals exposed to similar chemical denervation but maintained on a control diet exhibited well-documented "supersensitive" behavioral responses to apomorphine: N.Acc. denervated animals demonstrated increases in ambulatory sniffing, rearing and locomotor activity; CN-denervated animals demonstrated increases in rearing and focused sniffing in one location but no increases in locomotor activity. Compared to these control-fed animals, Li-diet animals receiving either CN- or N.Acc-denervation demonstrated a significantly decreased "supersensitive" behavioral response to apomorphine. N.Acc.-denervated animals receiving Li showed less apomorphine-induced locomotor activity. CN-denervated animals receiving Li showed less focused behavior which became evident as actual increases in locomotor activity after apomorphine. These results suggest that chronic dietary Li modifies postsynaptic mechanisms to suppress elements of the behavioral manifestations of supersensitive mesolimbic and nigrostriatal DA activity.

Animals↗
PubMed1960

The effect of temperature on the direct muscle twitch response and the action of drugs on the isolated denervated rat diaphragm.

The effect of temperature on the direct twitch response of the normal and denervated rat diaphragm, and the sensitivity of the contractural response of the denervated muscle to acetylcholine, suxamethonium, decamethonium, and potassium salts, was studied. Cooling the normal diaphragm from 39 to 20 degrees increased the size of the direct twitch, but below this temperature the twitch response of the muscle was progressively depressed. The denervated muscle twitch was, by contrast, maximal at 39 degrees and decreases as the temperature was lowered. This property of the denervated muscle first appeared about the third day after denervation. The contractural response of the denervated diaphragm to applied acetylcholine was enhanced by cooling, while the response to potassium salts was depressed. The depression of the contracture induced by potassium followed closely the depression of the direct muscle twitch of the denervated muscle over the same temperature range.

Acetylcholine↗