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Results for “Microinjection”

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At least 217 records · Page 12Linked to original sources

PubMed1994

Effect of dynorphin microinjection in the paraventricular nucleus on the hemodynamic response to hemorrhage in the rat.

We studied the effect of dynorphin A-(1-13), dynorphin A-(1-17), des-tyr dynorphin A-(2-17) (inactive at opioid receptor) or normal saline (NS) microinjected into the paraventricular nucleus (PVN) (n = 9/treatment) on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and left ventricular stroke work (LVSW) during fixed-volume hemorrhage in conscious rats. Microinjection of dynorphin A-(1-13) (6 nmol) into PVN at 15 min following the termination of fixed volume hemorrhage (8 ml/300 g) significantly decreased MAP from 50 min to 2 hr postinjection (P < 0.05 compared to animals receiving NS), while dynorphin A-(1-17) (6 nmol) significantly decreased MAP from 30 min up to 2 hr postinjection (P < 0.05). Microinjection of des-tyr dynorphin A-(2-17) (6 nmol) into the PVN did not significantly affect MAP following hemorrhage. Recovery of MAP in the dynorphin A-(1-13) and dynorphin A-(1-17) groups following hemorrhage was found to be significantly attenuated compared to the NS group (P < 0.05 and P < 0.01, respectively). Dynorphin A-(1-13) increased heart rate at 20 min and decreased stroke volume at 60 min after microinjection directly into the PVN following hemorrhage when compared with the NS group (P < 0.05). Both dynorphin A-(1-13) and dynorphin A-(1-17) significantly decreased LVSW after PVN injection following hemorrhage compared to NS group (both P < 0.05). No significant effects were observed on CO following microinjection of active or inactive opioid peptides into the PVN following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of dynorphin microinjection in the anterior hypothalamus (AV3V) region on the hemodynamic response to hemorrhage in the rat.

The region surrounding the anteroventral part of the third ventricle (AV3V) is important for the regulation of cardiovascular homeostasis. In the present study we investigated the effect of the kappa-opioid receptor agonists dynorphin A-(1-17) and dynorphin A-(1-13) microinjected into the AV3V region on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and left ventricular stroke work (LVSW) during fixed-volume hemorrhage in conscious rats. During fixed-volume hemorrhage (8 ml/300 g), dynorphin A-(1-17) (6 nmol), microinjected into the AV3V, significantly decreased MAP up to 30 min postinjection (P < 0.05). Recovery of MAP, SV, and LVSW in the dynorphin A-(1-17) group following hemorrhage was found to be significantly attenuated compared to that in animals receiving microinjection of normal saline (NS) vehicle into the AV3V (P < 0.05). Hypothalamic microinjection of dynorphin A-(1-13) (6 nmol) also attenuated the recovery of SV following hemorrhage compared with the NS group (P < 0.05). No significant effects were observed on HR or CO following microinjection of dynorphin into the AV3V region. The results of this study suggest that activation of the kappa-opiate receptor system in the AV3V region of the hypothalamus can attenuate the compensatory cardiovascular responses to hemorrhage.

Animals↗

PubMed1993

Simultaneous pontine and basal forebrain microinjections of carbachol suppress REM sleep.

This study was performed to test the hypothesis that cholinoceptive basal forebrain systems can significantly influence cholinoceptive pontine mechanisms known to be important for generating rapid eye movement (REM) sleep. This hypothesis was examined by microinjecting the cholinergic agonist carbachol or saline (vehicle control) into the pons, the basal forebrain, or simultaneously into the pons and basal forebrain, while quantifying the effects on sleep and wakefulness in unanesthetized, chronically instrumented cats. All microinjections were made during wakefulness and were followed by 2 or 4 hr of recording. Polygraphic records were scored for wakefulness, non-REM sleep, REM sleep, and the REM sleep-like state evoked by pontine administration of carbachol (DCarb). Dependent variables quantified following each microinjection included the percentage of recording time spent in each state, the latency to onset of non-REM, REM, and DCarb, the number of episodes per hour of each state, and the duration of the longest episode of each state. A total of 149 microinjections were made into 15 forebrain and 11 pontine sites in eight cats. Basal forebrain administration of carbachol significantly increased wakefulness. Pontine microinjection of carbachol produced a state that polygraphically and behaviorally resembled REM sleep. This REM sleep-like state occurred in amounts significantly greater than natural REM sleep. Pontine carbachol also significantly decreased wakefulness and non-REM sleep. Simultaneous injection of carbachol into the pons and basal forebrain enhanced REM sleep, but the magnitude of this enhancement was significantly less than the increase in REM sleep evoked by carbachol injection into the pons alone. The results show that cholinoceptive regions of the basal forebrain can increase wakefulness and reduce the ability of pontine carbachol to evoke the REM sleep-like state. These findings suggest that basal forebrain administration of carbachol activates an arousal-generating system that can successfully compete with the powerful cholinergic REM sleep-generating system of the pons.

Animals↗

PubMed1993

Microinjection of L-lactate in the preretinal vitreous induces segmental vasodilation in the inner retina of miniature pigs.

PURPOSE: The authors investigated the hypothesis that the retinal vasomotor effect of acute hypoxia is mediated by lactate. METHODS: Retinal vasomotor arteriolar response was measured in the intact eyes of miniature pigs after systemic administration and after local preretinal juxta-arteriolar microinjection of lactate. RESULTS: Injection of L-lactate (physiologically produced lactate) into the systemic circulation decreased the arterial blood pH but did not dilate the retinal arterioles. By contrast, microinjections of L-lactate (0.5 mol/l, pH 2) into the juxta-arteriolar vitreous induced a reversible segmental vasodilation of 32 +/- 4% (standard deviation). This vasodilation did not depend on periarteriolar pH lowering because microinjections of a 0.5 mol/l L-lactate at neutral pH also dilated segmentally the retinal arterioles (37 +/- 5.5%). The effect of lactate was stereospecific because microinjections of the isomer D-lactate (0.5 mol/l, pH 2) did not affect the arteriolar caliber (P = 0.63). Perfusion of the eye with the cyclo-oxygenase inhibitor indomethacin, through cannulization of the sublingual artery, caused a generalized reversible arteriolar vasoconstriction of 51 +/- 9.8% but did not inhibit the segmental vasodilator effect of locally microinjected L-lactate. CONCLUSIONS: It is known that acute hypoxia in the isolated retina causes an increase in lactate production. In the intact eye, there is a retinal vasodilation, which is not inhibited by indomethacin. Hence, it was concluded that retinal, but not blood, lactate is a possible mediator of the acute hypoxia-induced vasodilation.

Animals↗

PubMed1995

Glycine blocks the pressor response to L-glutamate microinjected into the nucleus tractus solitarii of conscious rats.

Microinjection of L-glutamate into the nucleus tractus solitarii (NTS) of conscious freely moving Wistar rats (240-260 g) produces pressor (+48 +/- 4 mmHg) and bradycardic (-153 +/- 20 bpm) responses. In the present study L-glutamate (2.5 nmol/100 nl) was microinjected before and after microinjection of increasing doses of glycine (10, 25 and 50 nmol/100 nl, N = 6) or saline (vehicle/100 nl, N = 6) into the NTS. Microinjections of increasing doses of glycine into the NTS produced a dose-dependent reduction in the pressor but not in the bradycardic responses to L-glutamate. [10 nmol (+29 +/- 5 mmHg and -110 +/- 18 bpm), 25 nmol (+12 +/- 7 mmHg and -88 +/- 21 bpm) and 50 nmol (+4 +/- 2 mmHg and -100 +/- 31 bpm)] The dose-dependent blockade of the pressor response to L-glutamate by glycine suggests an inhibitory neuromodulatory role for this amino acid in the sympatho-excitatory activity produced by L-glutamate microinjection into the NTS.

Animals↗

PubMed1997

Microinjection of bivalve eggs: application in genetics.

New strategies for embryonic manipulation have been developed in recent years through plant and animal research. However, research on marine invertebrate embryos has suffered from a lack of basic tools, such as microinjection. Here we present a technique developed for microinjecting eggs and embryos of the oyster Crassostrea gigas and the mussel Mytilus edulis. In experimental trials, approximately 40% of microinjected embryos survived. This technique was used to microinject beta-galactosidase, for which specific detection techniques were developed. A reporter construct (CMV-beta) based on a promoter of cytomegalovirus linked to the beta-galactosidase-encoding gene was then microinjected, and the expression level of this construct was monitored. The suitability of this technique is discussed in terms of its application to the manipulation of bivalve mollusks in pathology and genetics.

Animals↗

PubMed1997

Cytoplasmic transport in Drosophila ovarian follicles: the migration of microinjected fluorescent probes through intercellular bridges depends neither on electrical charge nor on external osmolarity.

Using video-intensified fluorescence microscopy and a pseudocolor display of fluorescence intensity, we analyzed the distribution of microinjected molecules within the nurse-cell/oocyte syncytium of Drosophila ovarian follicles. We varied the composition and the osmolarity of the culture solution as well as the electrical charge and the molecular mass of the microinjected fluorescent probe. As culture solutions, we used four simple salines (IMADS) and a complex tissue-culture medium (R-14) that matched the osmolarity of adult hemolymph. Small amounts of two anionic dyes (Lucifer Yellow CH and Lucifer Yellow dextran) as well as of two cationic dyes (rhodamine 6G and tetramethylrhodamine dextran-lysine) were iontophoretically microinjected either into a nurse cell or into the oocyte of stage-10 follicles. In the tissue-culture medium, within a few seconds following microinjection, all tested dyes passed through the intercellular bridges in both the anterior direction (to the nurse cells) and the posterior direction (to the oocyte), independent of their electrical charge or molecular mass. In all simple salines, irrespective of their osmolarity, Lucifer Yellow CH was found to preferentially migrate in the posterior direction and to accumulate in the oocyte due to progressive binding to yolk spheres. Thus, with this sensitive method, no correlation was detectable between the external osmolarity, the electrical charge and the preferential direction of migration of a microinjected probe. Our results indicate that the electrical gradient described by other authors does not exert significant influence on the migration of charged molecules through intercellular bridges in situ.

Animals↗

PubMed1997

Transfer of macromolecules into living adult cardiomyocytes by microinjection.

Among techniques commonly used to deliver bioactive molecules into living cells, microinjection is a very efficient method. Microinjection has been used extensively for gene transfer into different cell types. We applied the microinjection technique to the adult rat ventricular cardiac muscle cells (AVC) in primary culture and optimized microinjection parameters and the appropriate cell culture conditions. We also optimized the use of particular agents (i.e. 2,3-butanedione monoxime, verapamil) for the prevention of the cell damage caused by the micropuncture. We obtained the expression of a CMV-beta-galactosidase reporter gene in up to 20% of the injected cells with efficient maintenance of long term cell viability. Under our experimental conditions direct microinjection is a very advantageous technique to transfer macromolecules into living adult cardiac muscle cells and a powerful system to study and manipulate the biochemistry and molecular biology of the cardiac myocyte.

Age Factors↗

PubMed1999

Timing of DNA integration, transgenic mosaicism, and pronuclear microinjection.

Selection of transgenic embryos prior to embryo transfer is a means to increase the efficiency of transgenic livestock production. Among transgenic reporters, cytoplasmic expression of green fluorescent protein (GFP) has features that make it ideal for transgenic embryo selection. The primary objective of this study was to assess cytoplasmic expression of a specially designed GFP reporter as a tool for transgenic bovine embryo selection. A second objective was to evaluate this reporter for studying transgenic mosaicism related to timing of integration of pronuclear microinjected DNA. Transgenic embryos produced by pronuclear injection showed a discrete pattern of GFP expression with clusters at 25, 50, and 100% of blastomeres expressing GFP. This pattern of mosaicism is interpreted to indicate that the integration of microinjected DNA occurred, not only at the pronuclear stage, but also in the subsequent cell divisions. Among the GFP-positive transgenic embryos, only in 21% did all the blastomeres show the green fluorescence. Using the fraction of positive blastomeres within an embryo, the timing of integration of microinjected DNA was estimated. The frequency of nonmosaic embryos expressing GFP is consistent with published germline transmission success rates of transgenic cattle derived from pronuclear microinjected embryos. These results indicate the possible application of GFP as a marker of transgenic embryos and graphically illustrate underlying complexities in DNA integration in embryos subjected to pronuclear microinjection.

Animals↗

PubMed1993

Expression of endogenous and microinjected hsp 30 genes in early Xenopus laevis embryos.

In the present study, we have examined the regulation of expression of a newly isolated member of the hsp 30 gene family, hsp 30C. Using RT-PCR, we found that this gene was first heat-inducible at the tailbud stage of development. We also examined the expression of two microinjected modified hsp 30C gene constructs in Xenopus embryos. One of the constructs had 404 bp of hsp 30C 5'-flanking region, whereas the other had 3.6 kb. Both gene constructs had 1 kb of 3'-flanking region. RT-PCR assays were employed to detect the expression of these microinjected genes. The presence of extensive 5'- and 3'-flanking regions of the hsp 30C gene did not confer proper developmental regulation, since heat-inducible expression of both of the microinjected constructs was detectable at the midblastula stage. The premature expression of the microinjected hsp 30 gene was not a result of high plasmid copy number of the presence of plasmid DNA sequences. These results suggest that the microinjected genes contain all the cis-acting DNA sequences required for correct heat-inducible regulation but do not contain the elements required for the proper regulation of hsp 30 gene expression during development. It is possible that regulatory elements controlling the developmental expression of the hsp30 genes may reside upstream or downstream of the entire cluster.

Animals↗

PubMed1979

Inhibition of spinal cord interneurons by narcotic microinjection and focal electrical stimulation in the periaqueductal central gray matter.

Single cell evoked activity was recorded from spinal cord interneurons in rats prepared with microinjection cannulae or stimulating electrodes in the periaqueductal central gray matter (PAG). Morphine microinjections (4-16 microgram) inhibited the response evoked by a noxious stimulus in 55% of the wide dynamic range neurons tested. Microinjections of etorphine (0.25-0.5 microgram) inhibited 82% of the nociceptive neurons tested. Neither drug inhibited neurons which responded only to innocuous mechanical stimulation. The inhibition of wide dynamic range neurons produced by narcotic microinjection was antagonized by naloxone (1 mg/kg, i.p.) in 7 of 11 cases. Control experiments indicated that the effects obtained with microinjections could not be attributed to the drugs' diffusion to the spinal cord. Focal electrical stimulation of the PAG inhibited the responses to noxious stimuli of 60% of wide dynamic range neurons but was without effect on the responses of neurons that were activated only by innocuous stimuli. These experiments directly demonstrate that narcotic analgesics restricted to an intracerebral site of action activate a neural system which preferentially inhibits the responses of spinal cord wide dynamic range neurons to noxious stimuli. The system has a specificity for nociceptive input since non-nociceptive neurons were unaffected. Directly comparable results were produced by electrical stimulation of the PAG, supporting the concept that stimulation and narcotics modulate the transmission of nociceptive information by similar mechanisms.

Animals↗

PubMed1980

Microinjection of morphine within nucleus raphe magnus and dorsal horn neurone activities related to nociception in the rat.

The hypothesis of an increase by morphine of descending inhibitory controls acting upon the transmission of painful messages at the spinal level has been directly investigated in intact anaesthetized rats. The analgesic efficacy of morphine microinjections (5 micrograms in 0.2 microliter saline) applied within the nucleus raphe magnus (NRM) was examined using the threshold for vocalization after electric shock to the tail as a test: a mean threshold increase of 57% was observed. A few days later, the effects of similar microinjections upon dorsal horn cell activities were studied in acute experiments in the same animals. The response of dorsal horn convergent units induced by the activation of large myelinated (Aa) afferent fibres were unaffected by the microinjection of morphine within the NRM. In the case of the responses of convergent units induced by the activation of unmyelinated (C) afferent fibres, two different results were obtained after microinjection of morphine within the NRM: 8/14 units were not affected and 6/14 were clearly excited. A transient reversal of the excitatory effects was observed after the systemic administration of the opiate antagonist naloxone. The responses of marginal layer cells (lamina 1) were unaffected by the microinjection of morphine within the NRM. These unexpected results are discussed in view of the fact that they conflict with current concepts regarding morphine analgesia.

Animals↗

PubMed1986

Comparison of the antinociceptive action of mu and delta opioid receptor ligands in the periaqueductal gray matter, medial and paramedial ventral medulla in the rat as studied by the microinjection technique.

In rats stereotaxically implanted with microinjection cannula in either the periaqueductal gray matter (PAG) or the medial/paramedial medullary reticular formation (MRF), microinjection of morphine, sufentanil, D-Ala2-D-Leu5-enkephalin (DADL) or D-Ser2-Thr6-leucine enkephalin (DSTLE) produced dose-dependent elevations in the response latency on tail-flick and hot plate tests. These effects were reversed by naloxone administered by microinjection into the same intracerebral site. Both mu (morphine and sufentanil) and delta (DADL and DSTLE) opioid receptor ligands produced a maximal elevation in the supraspinally mediated hot plate response when administered into either the PAG or the MRF. Similarly, mu and delta receptor ligands produced maximum elevations in the spinally mediated tail-flick response when microinjected into the PAG. In contrast, delta, but not mu, receptor agonists produced a total blockade of the tail-flick response following administration into the MRF. Microinjection of mu (morphine) or delta (DADL) agonists into the PAG or the MRF also resulted in a naloxone-reversible inhibition of the visceral chemical evoked writhing response. These observations suggest that mu and delta opioid receptor linked systems within the MRF but not the PAG produce their antinociceptive effects by discriminable mechanisms with a differential action on spinopetal vs supraspinal modulatory systems.

Analgesics, Opioid↗

PubMed1994

Use of F1 progeny of HolsteinxZebu cross cattle as oocyte donors for in vitro embryo production and gene microinjection.

This study was designed to determine the possibility of using F1 crossbreed cattle (HolsteinxZebu) as donors of oocytes for in vitro fertilization (IVF) and for pronuclear gene microinjection into in vitro-produced embryos. In the first part of the experiment oocytes from Bos taurus (Holstein), Bos indicus (Zebu) and F1 crossbred Bos taurusxBos indicus (HolsteinxZebu) genotypes were inseminated with Bos taurus (Holstein) semen and were allocated for in vitro embryo production using conventional IVF procedures. No differences were observed on the in vitro maturation (IVM) rates between breeds (HolsteinxHolstein:85%, ZebuxHolstein:84% and ZebuxHolsteinxHolstein:88%). Holstein cows yielded the highest number of cumulus oocyte complexes (6.8 per ovary) for in vitro maturation, differing (P<0.05) from ZebuxHolstein and ZebuxHolsteinxHolstein F1 by 5.1 and 5.8, respectively. However, the Holstein breed also yielded the lowest percentage of cleavage (45.1 vs 71.9% for ZebuxHolstein and 65.1% for ZebuxHolsteinxHolstein). Of the 3 genotypes, the hybrid F1 breed was the most efficient source of oocytes for the production of embryos capable of reaching morulae and blastocyst stages (76/250; P<0.001). In the second part of the study, 599 oocytes from the F1 breed were fertilized in vitro, 1 group of 150 oocytes was used for the determination of the optimal pronuclear visualization period. The highest number of oocytes with 2 pronuclei was observed between 24 to 28 h after IVF (27 to 42%). The remaining 399 oocytes were microinjected with a gene construct bearing the bacterial lacZ gene as the reporter for gene expression. Survival of embryos to microinjection was 73.8%, and 45.5% of them (50/110) cleaved in culture. Of the microinjected embryos, 1 out of 50 showed beta-galactosidase activity. These findings indicate that a tropical crossbreed of cattle (ZebuxHolsteinxHolstein) can be used as a source of oocytes for IVF programs and gene microinjection studies.

Journal Article↗

PubMed2006

Microinjection of muscimol into caudal periaqueductal gray lowers body temperature and attenuates increases in temperature and activity evoked from the dorsomedial hypothalamus.

Microinjection of the neuronal inhibitor muscimol into the midbrain lateral/dorsolateral periaqueductal gray (l/dlPAG) suppresses increases in heart rate (HR) and mean arterial pressure (MAP) evoked by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) into the dorsomedial hypothalamus (DMH) in rats. Injection of BMI into the DMH also increases body temperature (Tco) and motor activity. Here, our goal was to extend previous findings by examining the effect of microinjection of muscimol into the PAG on these thermogenic and behavioral responses in conscious freely moving rats. Microinjection of muscimol (300 pmol and 1 nmol) alone into the l/dlPAG reduced baseline Tco without affecting activity, HR, or MAP. Similar injection of a dose that failed to alter baseline Tco (100 pmol) suppressed the increases in Tco evoked from the DMH and significantly attenuated DMH-induced increases in locomotor activity. Whereas microinjection of 1 nmol muscimol into the ldlPAG abolished the increases in Tco evoked from the DMH and in fact lowered body temperature to a degree similar to that seen after this dose of muscimol alone, 1 nmol muscimol at adjacent sites outside the targeted region of the PAG had no significant effect on DMH-induced increases in Tco or any other parameter. These results indicate a role for neuronal activity in the l/dlPAG in (1) the temperature and behavioral responses to disinhibition of neurons in the DMH, and (2) the maintenance of basal body temperature in conscious freely moving rats.

Animals↗

PubMed1992

Neuroethological evaluation of audiogenic seizures and audiogenic-like seizures induced by microinjection of bicuculline into the inferior colliculus. I. Effects of midcollicular knife cuts.

Audiogenic seizures (AS) are a model of generalized tonic-clonic seizures. The inferior colliculus (IC) and the GABAergic neurotransmission seems to be the most critical site and neurotransmitter system, respectively, of the auditory midbrain involved in AS origin and development. Thus, audiogenic-like seizures are evoked by GABAA antagonists such as bicuculline (BIC). Wistar audiogenic AS resistant (R) rats were sham-transected through the midcollicular line and microinjected with IC bicuculline (BIC; 80 ng/0.2 microliters) (n = 8); transected through the midcollicular line and microinjected with IC saline 0.9% (n = 8); transected through the cortex above the midcollicular line and microinjected with IC BIC (n = 3); transected through the midcollicular line up to 6.0 mm depth and microinjected with IC BIC (80 ng/0.2 microliters or 120 ng/0.3 microliters (n = 8). Wistar AS susceptible (S) rats were submitted to cortical transections (n = 8) and midcollicular transections (n = 7). Animals were studied by means of an ethological method before and after microinjections and/or transections in order to evaluate possible pathways in the AS-like evoked seizures. Bicuculline-evoked seizures were very similar to those evoked by acoustic stimulation, but lacked the tonic-clonic component. No modification in animal behavior was observed in the presence of sound, once the AS-like behavior was initiated. A small percentage of the animals, however, presented procursive behavior which was increased by sound. The IC BIC-evoked patterns were almost totally blocked by midcollicular but not cortical transections. Furthermore, midcollicular but not cortical transections blocked the tonic-clonic component of AS in genetically S animals without modifying the wild running component. These data suggest that the inferior colliculus-superior colliculus connection may be involved in the sensorimotor transduction necessary for AS-like behaviors.

Acoustic Stimulation↗

PubMed1970

Microinjections of tubocurarine, leptazol, strychnine and picrotoxin into the cerebral cortex of anaesthetized cats.

1. In cats anaesthetized with intravenous chloralose, microinjections of tubocurarine, leptazol, strychnine or picrotoxin, in a volume of 1 mul, were made into the grey matter of the cerebral cortex and the electrical activity was recorded from the site of injection with the microinjection cannula which, insulated except at its tip, served as recording electrode.2. Routinely the injections were made into the gyrus splenialis or into the underlying gyrus cinguli close to the mid-line, because the injections would then most likely be in grey and not in white matter. Injected in this way all four drugs set up foci of excitation which gave rise to synchronous firing of a large number of neurones with the result that high voltage negative spikes were recorded from the microinjection cannula.3. On injection into the gyrus splenialis the threshold dose was about 0.04 mug for picrotoxin, about 0.2 mug for tubocurarine, about 5 mug for strychnine and 25 to 50 mug for leptazol. Following the injection of larger doses the spike discharge continued for a few hours after picrotoxin and tubocurarine, for over an hour after strychnine, but for a few minutes only after leptazol. On injection into the gyrus cinguli the threshold doses were slightly greater and with larger doses the spikes occurred at greater frequency but were of lower voltage than in the gyrus splenialis.4. With large doses of picrotoxin injected into the gyrus splenialis the spikes developed an after-positivity and an after-discharge which sometimes passed into a short period of fast activity.5. The foci of excitation set up by the drugs were restricted to the site of injection because on raising or lowering the microinjection cannula the spikes recorded from it quickly decreased in voltage and then disappeared. When the injections were made close to a sulcus and the microinjection cannula, on being lowered, traversed the sulcus, the spikes changed their polarity.6. The spike discharge appears to be a consistent response to the injections of the drugs into grey matter of any part of the cerebral cortex since it was also obtained on their injection into the pyriform cortex, amygdala and area retrolimbica anterior, but not on their injection into white matter or caudate nucleus, thalamus or hypothalamus.

Action Potentials↗

PubMed1983

The relative significance of spinal and supraspinal actions in the antinociceptive effect of morphine in the dorsal horn: an evaluation of the microinjection technique.

Large quantities of morphine injected directly into the brainstem of spinal anaesthetized cats inhibited the noxious heat-evoked excitation of dorsal horn neurones. The amounts required were similar to those that were required intravenously in cats with the spinal cord intact or transected. When the spinal cord was intact the amount of morphine microinjected into the brainstem required to inhibit the excitation of dorsal horn neurones was about ten fold less than it was in spinal animals. It is concluded that large, but not small doses of morphine microinjected into the brainstem can exert effects on the spinal cord after first entering the circulation. The effects of small doses are attributed to a local action in the brainstem which causes inhibition of spinal neurones either by activating descending inhibitory neuronal systems or by liberating endogenous substances which reach the spinal cord via the cerebro-spinal fluid. The concentrations of morphine achieved at various distances from the site of injection by the microinjection of microgram quantities and the time courses of the concentration changes were calculated from diffusion equations, assuming diffusion coefficients of 3 or 5 X 10(6) cm2 s-1. The curves obtained closely approximated those obtained experimentally. The concentrations achieved at distances up to 2 mm from the site of injection of 10 micrograms of morphine were calculated to exceed 10(-4)M and the time-courses of these concentration changes were compatible with the time course of inhibition of spinal neurones, or the production of analgesia after microinjection. Such concentrations are vastly in excess of those achieved in the brain after the systemic administration of morphine in analgesic doses. It is concluded that the local effects in the brainstem produced by the microinjection of microgram quantities of morphine have no relevance to the mechanism of analgesia produced by systemic administration.

Animals↗