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C Advokat

Publications and source records attributed to C Advokat.

At least 37 records · Page 2Linked to original sources
PubMed1991

Spinal transection reduces both spinal antinociception and CNS concentration of systemically administered morphine in rats.

Within one day after spinal transection, the antinociceptive effect of systemically administered morphine on the spinal withdrawal reflex is significantly reduced. This observation has provided important empirical support for the present model of opiate-induced analgesia. One prediction from this model is that the antinociceptive effect of intrathecal (spinal) morphine injections should not be reduced by spinalization. When examined experimentally, this prediction was not supported; the antinociceptive effect of intrathecally administered morphine was significantly enhanced after acute spinalization. This result suggested an alternate hypothesis of morphine-induced analgesia. One prediction from this new hypothesis is that the decreased behavioral response to systemic morphine in spinal rats is due to a decrease in the spinal concentration of morphine produced by spinal transection. To test this prediction separate groups of intact rats and acute (one day) spinal rats, were assessed with the tail-flick (TF) procedure 60 min after subcutaneous injection of various doses of morphine (0.75, 1.5, 3.0, 4.5, 6.0 or 9.0 mg/kg) or at different time points (30, 60, 90, 150 or 240 min) after a single injection of 9.0 mg/kg. Immediately after behavioral testing, the rats were killed and brains, spinal cords and blood samples were collected and subsequently analyzed with a morphine radioimmunoassay. The results show that the concentration of morphine in the brain and spinal cords of acute spinal rats is significantly lower than that of intact rats, whereas morphine levels in the blood do not differ. These data suggest that the decreased antinociceptive effect of subcutaneous morphine in acute rats is due to a decrease in the concentration of the opiate in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Is tolerance to intrathecal morphine in intact rats supraspinally mediated?

The effect of repeated intrathecal (IT) injections of 5 micrograms of morphine on the tail flick (TF) was determined in rats that were tested either 0.5 h or 5.0 h after administration on each of five successive days. Tolerance developed rapidly in animals tested 5.0 h after each injection. Animals tested 0.5 h after each injection did not become tolerant. Animals that were tested 5.0 h after an intrathecal saline injection on the first four days were also tolerant to a 5 micrograms dose of morphine on the fifth day. These data are discussed in the context of previous conflicting reports concerning tolerance to intrathecal morphine. It is suggested that, under certain conditions, tolerance to intermittent intrathecal morphine administration may be due to a supraspinal opiate action.

Analgesics↗
PubMed1990

Tolerance to the antinociceptive effect of intrathecal morphine in intact and chronic spinal rats.

The antinociceptive effect of daily acute intrathecal morphine injections on the tail-flick withdrawal response was compared in Intact rats and rats that were spinally transected 3 to 4 weeks prior to morphine administration (Spinal rats). Spinal rats became tolerant to repeated intrathecal injections of 5, 15, or 30 micrograms of morphine within 3 days. Intact rats were not tolerant to these doses after 4 daily injections. Spinal rats, made tolerant to repeated intrathecal morphine injections, were not tolerant to a subcutaneous injection of 6.0 mg/kg of morphine. These data suggest that, in intact animals, tolerance to the antinociceptive effect of spinal morphine is modulated by descending, supraspinal input.

Animals↗
PubMed1989

The synergistic effect of concurrent spinal and supraspinal opiate agonisms is reduced by both nociceptive and morphine pretreatment.

The antinociceptive effect of morphine administered into the periaqueductal gray (PAG), the intrathecal space (ITH) and concurrently, into both sites (in a 1:1 dose ratio), was assessed in 1) nontolerant rats, 2) rats made tolerant to the effect of morphine on the tail-flick (TF) test and 3) rats that were tested on the TF during chronic saline administration. In nontolerant rats, concurrent morphine injections produced a multiplicative antinociceptive effect (ED50 = 0.392 microgram, total dose) relative to that obtained after separate PAG (ED50 = 2.8 micrograms) or ITH (ED50 = 6.7 micrograms) injections. The multiplicative effect of concurrent morphine administration was significantly reduced in rats made tolerant to morphine (one 3 mg/kg SC injection and TF test per day for six days). Opiate synergy was also reduced but to a smaller extent in rats that were repeatedly tested on the TF during chronic saline administration (one SC injection and TF test per day for six days). Neither chronic morphine nor saline pretreatment altered the dose-response function to intrathecal morphine. However, both morphine and saline pretreatment significantly reduced the antinociceptive effect of morphine administered into the PAG. The data indicate that concurrent morphine administration into the PAG and ITH space results in a synergistic antinociceptive action which is reduced by performance of the nociceptive response, even in the absence of opiate administration. We suggest that the decrease in opiate synergism produced by nociceptive assessment (behavioral tolerance) is mediated supraspinally, while the additional decline resulting from morphine administered in conjunction with the nociceptive tests (opiate tolerance) is mediated by a combined action at spinal and supraspinal sites.

Animals↗
PubMed1989

Antinociceptive effect of intrathecal morphine in tolerant and nontolerant spinal rats.

The antinociceptive effect of intrathecal morphine on the tail-flick (TF) reflex of rats was significantly enhanced within one day after spinal transection (ED50 = 0.125 microgram) relative to the effect obtained in intact rats (ED50 = 5.9 micrograms). By 20-30 days after spinalization the potency of intrathecally administered morphine had substantially declined. Intact rats, made tolerant to the antinociceptive effect of systemic morphine (3.0 mg/kg, SC on each of seven consecutive days), were not tolerant to intrathecal morphine (ED50 = 6.5 micrograms). In contrast, rats that were pretreated with either morphine alone, repeated TF tests alone, or both of these treatments, were tolerant to intrathecal morphine when tested one day after spinal transection. The results suggest first, that the antinociceptive effect of intrathecal morphine in intact rats is tonically inhibited by descending supraspinal input and that removal of this input is responsible for the enhanced antinociceptive effect of intrathecal morphine in spinal rats. Second, the data suggest that tolerance to the antinociceptive effect of intrathecal morphine in intact rats may also be tonically inhibited by supraspinal input, because spinal opiate tolerance is expressed after spinal transection.

Anesthetics↗
PubMed1989

Tolerance to the antinociceptive effect of morphine in spinally transected rats.

The effect of a spinal transection on morphine-induced tolerance in rats was examined with the tail withdrawal reflex (tail flick; TF), elicited by noxious thermal stimulation. Intact rats became tolerant to sc morphine injections (3.0 mg/kg) if they were tested on the TF after each injection. Morphine administration alone did not produce tolerance; tail flick tests alone did, though not always to a significant extent. However, when morphine only, TF tests only, or both were administered prior to transection (acute spinal rats), all groups were tolerant when tested 1 day after spinalization. When the same treatments were administered to rats 3 weeks after spinal transection (chronic spinal rats), neither morphine nor TF tests alone produced tolerance. Chronic spinal rats became tolerant only if they were tested after each injection. These results suggest, first that tolerance develops at the spinal cord as a result of either chronic opiate exposure or performance of the nociceptive response but that, intact rats, tolerance is inhibited or suppressed by a supraspinal action of morphine. Second, the fact that chronic spinal rats did not become tolerant to morphine or TF tests alone suggests either that such tolerance is mediated by descending input or that spinal transection produces intrinsic changes in the spinal cord that preclude the development of tolerance induced only by opiate or behavioral stimulation.

Animals↗
PubMed1987

Tolerance to morphine microinjections in the periaqueductal gray (PAG) induces tolerance to systemic, but not intrathecal morphine.

The acquisition and retention of tolerance to the antinociceptive effect of supraspinal morphine on the tail withdrawal reflex was assessed in rats implanted with unilateral cannulae in the periaqueductal gray (PAG). Development of tolerance to daily microinjections of morphine was indicated by the return of the tail flick response within 4 days, followed by the recovery of analgesic sensitivity one week later. After tolerance had developed, the effect of an acute systemic (1.5-4.5 mg/kg) or intrathecal (5-15 micrograms) morphine injection was determined. 'Cross-tolerance' was observed between systemic and supraspinal morphine but not between intrathecal and supraspinal morphine. The data indicate that tolerance to chronic intracerebral morphine produces the same behavioral consequences as tolerance to systemic morphine.

Animals↗
PubMed1987

Antinociceptive effect of systemic and intrathecal morphine in spinally transected rats.

The antinociceptive effect of morphine on the tail withdrawal reflex was examined in spinally transected rats. The efficacy of systemically administered morphine was significantly reduced within 24 h after transection, and continued to decline during the first three posttransection weeks. In contrast to the diminished effect of systemic morphine, the efficacy of intrathecal morphine was not reduced during the first three weeks after a spinal transection. These data demonstrate a significant difference in the functional effect of systemic and spinal morphine in spinally transected rats. The results indicate that the direct antinociceptive effect of morphine on the spinal cord is not reduced after spinal transection.

Analgesics↗
PubMed1987

Investigation of tolerance to chronic intrathecal morphine infusion in the rat.

Rats received chronic subcutaneous or intrathecal infusions of either saline or 25 micrograms/microliter/hr or 50 micrograms/microliter/hr of morphine sulfate. During five days of infusion individual groups of rats were assessed on either the nociceptive tail flick or hot plate test. After the infusions, the analgesic effects of either subcutaneous or intrathecal morphine test doses were evaluated. Tolerance developed to the analgesic effect of both subcutaneous and intrathecal morphine infusions on the tail flick test. Subcutaneously infused rats were also tolerant to a subcutaneous morphine challenge on this test. However, intrathecally infused rats were not tolerant to either the subcutaneous or intrathecal challenge. In contrast to these results, rats tested on the hot plate were not analgesic in response to either subcutaneous or intrathecal morphine infusions. However, these rats were tolerant when challenged with either subcutaneous or intrathecal morphine. The results are discussed in terms of the relative contribution of spinal and supraspinal sites to opiate tolerance, and the possibility that tolerance does not develop to the antinociceptive effect of spinal morphine on spinally mediated reflexes.

Animals↗
PubMed1986

Investigation of "cross-tolerance" between systemic and intrathecal morphine in rats.

Animals were implanted subcutaneously with morphine or placebo pellets and assessed daily on the hot plate or the tail flick test. After tolerance developed to morphine-induced analgesia the response to an acute systemic (1-6 mg/kg SC) or intrathecal morphine injection (0-30 micrograms) was determined. "Cross-tolerance" was observed on both the hot plate (6 mg/kg) and the tail flick tests (3 and 6 mg/kg) between the two different routes of subcutaneous administration. "Cross-tolerance" was also observed between systemic and intrathecal morphine on the hot plate test. However, no "cross-tolerance" between systemic and spinal morphine was observed in animals on the tail flick test. Assessment of naloxone-precipitated withdrawal indicated that morphine implanted animals showed more abstinence signs (wet shakes and teeth chattering) than placebo animals. These results suggest that the nociceptive assessment procedure plays a significant role in the expression of "cross-tolerance" between systemic and spinal opiates.

Animals↗
PubMed1986

Effects of ethanol on gastrointestinal transit in mice.

The acute effects of ethanol on gastrointestinal transit were studied in mice. Intraperitoneal injection of 2 or 3 g of ethanol/kg had a dose-dependent inhibitory effect on gastrointestinal transit. Subcutaneous injection of 4 g of ethanol/kg also inhibited gastrointestinal transit, but this route was less effective than the intraperitoneal route of administration. Further examination of both the time course of inhibition and the weight of the stomach contents suggested that intraperitoneal injections of moderate doses of ethanol did not alter gastric emptying. The data indicated that gastrointestinal transit is inhibited by ethanol and that the most sensitive locus is the small intestine rather than the stomach.

Animals↗
PubMed1985

Motor paralysis in rats after repeated electroconvulsive shock: comparison between aural and corneal stimulation.

Daily transaural electroshock treatment of rats results in a reversible hindlimb paralysis. Assuming there is a relationship between current pathway and the route of electroshock administration we compared both the type of convulsive behavior and the incidence of paralysis produced by transcorneal shock with that of transaural stimulation. Both transaural and transcorneal stimulation induced clonic and tonic convulsions, whereas, only transaural stimulation induced a body flexion (twisting and writhing). The use of transaural electrodes induced a higher incidence of paralysis than the use of corneal electrodes. These data demonstrate that both (1) the type of convulsive behavior produced and (2) the incidence of paralysis is related to electrode placement suggesting that paralysis is a function of current pathway.

Animals↗
PubMed1985

Evidence of place conditioning after chronic intrathecal morphine in rats.

The acute administration of either systemic or intrathecal morphine produced an antinociceptive reaction on the tail flick test; only systemic morphine produced a sedative effect on motor activity. Rats receiving chronic intrathecal injections were hyperactive relative to saline injected control subjects. After a series of four injections, a place preference was induced by both routes of administration: rats who had previously received morphine either by subcutaneous or intrathecal injection spent significantly more time in the context in which the drug had been given, relative to rats who were comparably injected with saline. These data suggest that chronic intrathecal morphine in rats may elicit a discriminable cue, either through direct pharmacological stimulation of supraspinal sites, or, indirectly, as a consequence of spinal opiate action.

Animals↗
PubMed1984

Reversible motor paralysis in rats after repeated electroconvulsive shock.

Repeated electroconvulsive shocks (ECS) delivered at brief (10 to 15 min) intervals through earclip electrodes, induced a reversible motor paralysis in 35% of treated rats. Paralysis was characterized by loss of locomotor activity without apparent loss of sensory functions. It occurred after 10 to 13 shocks regardless of whether stimulation was of subthreshold (40 to 60 mA) or suprathreshold (65 mA) intensity. This phenomenon may provide a useful animal model for the investigation of reversible injury to the spinal cord.

Animals↗
PubMed1983

Nociceptive assessment modifies behavioral tolerance without altering brain morphine concentration.

The influence of nociceptive assessment on the development of behavioral tolerance and on brain morphine concentration was examined in morphine pellet-implanted rats. Tolerance was facilitated by experience with the nociceptive tail flick test procedure, whereas whole brain opiate levels, determined by radioimmunoassay, were not altered by the behavioral tests. Parallel experiments with placebo-implanted rats indicate the significance of environmental context in nociception. These results demonstrate that behavioral manipulations can significantly modify pharmacological effects without altering drug concentration in the brain.

Analgesia↗
PubMed1983

Effect of environmental novelty and electroconvulsive shock on the tail flick reflex after placebo or morphine pellet implants.

After implantation of either a placebo or morphine pellet, different groups of rats were either assessed or not assessed on the nociceptive tail-flick test. After 1 week, latencies of placebo-implanted rats were significantly increased if the animals were inexperienced with the nociceptive test or if they were unfamiliar with the environment in which the test was administered. Latencies were not altered by an electroconvulsive shock (ECS) administered 1 week before the reflex test. In contrast, latencies of morphine-pretreated rats were not altered by prior experience with the nociceptive test per se. However, latencies of animals with prior test experience were modified by environmental novelty and ECS. Rats who became tolerant to morphine in a familiar environment were hyperalgesic when subsequently tested in unfamiliar surroundings. The latencies of rats who received a single ECS during the development of tolerance were unchanged 1 week later, whereas the latencies of rats who did not receive ECS showed a significant decline during this interval. These data demonstrate the mutual contribution of pharmacological and environmental variables in nociceptive behavior.

Animals↗