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Biomedical subjects

T A Rudy

Publications and source records attributed to T A Rudy.

At least 37 records · Page 2Linked to original sources
PubMed1977

A dose ratio comparison of the interaction between morphine and cyclazocine with naloxone in rhesus monkeys on the shock titration task.

Dose-response curves for morphine (0.5-20 mg/kg) were obtained in 4 rhesus monkeys performing the discrete trials shock titration task. Naloxone (5-500 microgram/kg) uniformly produced a dose dependent, parallel shift of the morphine dose-response curves to right. Plots for the 4 animals of the Log (dose ratio--1) versus --Log (naloxone) revealed that the line had a slope of -0.96. The value of the pA2 was 7.2. Similar experiments were carried out in two rhesus monkeys using cyclazocine. Naloxone (50-1000 microgram) similarly produced a rightward dose dependent, parallel shift of the cyclazocine dose response curves. Unlike the results obtained with morphine, the pA2 for naloxone obtained with cyclazocine was 6.3 and the slope of the dose ratio line was -1.6.

Animals↗
PubMed1977

Induction of tolerance and withdrawal in rats receiving morphine in the spinal subarachnoid space.

Rats implanted with chronic catheters in the spinal subarachnoid space were given twice daily injections for 7 days of morphine sulfate, either intrathecally into the lumbar subarachnoid space (15 or 50 microng) or i.p. (20 mg/kg). The development of tolerance, as manifested in a reduction of the analgetic efficacy of these injections on the hot plate and tail flick, occurred in a dose dependent fashion over a period of 7 days. At this time, injections of i.p. morphine into animals which had received spinal morphine and vice versa revealed the existence of a two way cross tolerance between spinal and systemically administered morphine. Injection of naloxone into the spinal cord of animals exposed to i.p. morphine or conversely, i.p. naloxone in animals tolerant to intrathecal morphine, yielded a hyperreflexia and extreme sensitivity to handling. Other signs commonly observed in percipitated withdrawal, however, such as wet shakes and weight loss, were not observed.

Analgesics, Opioid↗
PubMed1977

Studies on the antagonism by raphe lesions of the antinociceptive action of systemic morphine.

In rats, lesions were placed in the dorsal/median raphe (DMR), in the ventral raphe (VR: raphe magnus), in both the dorsal/median and ventral raphe (DMVR) or in the reticular formation (RF). The effect of the lesions on the antinociception and catalepsy produced by 3 doses of morphine (3, 10 and 30 mg/kg) was examined. The lesions had no significant effect on the catalepsy produced by any of the doses of morphine tested. DMR lesions produced a partial attentuation of the antinociceptive action of both the 3 and 10 mg doses. VR lesions produced a complete blockade of the 3 mg and only a partial attenuation of the 10 mg dose. In contrast, the combined (DMVR) lesions yielded virtually a total blockade of the 3 and 10 mg. Yet, as with the DMR and VR groups, the DMVR lesions failed to produce a significant antagonism on either of the nociceptive tests at the 30 mg dose. These findings suggest that the ascending and descending fiber systems emanating from the dorsal/median and ventral raphe, respectively, facilitate the expression of morphine-induced analgesia but that neither system alone can be regarded as essential for the manifestation of the antinociceptive effects of systematically administered morphine.

Analgesics, Opioid↗
PubMed1977

An extensive exploration of the rat brain for sites mediating prostaglandin-induced hyperthermia.

Experiments designed to ascertain the site or sites within the brain where prostaglandins act to evoke hyperthermia were carried out. At an ambient temperature of 20 degrees C, microinjections of PGE1 (50-100 ng) or saline vehicle were made in restrained rats. The 272 sites tested formed a matrix encompassing much of the subcortical tissue rostral to the medulla. The sensitivity of each site to PGE1 was evaluated on the basis of the dose required to elicit a criterion level of effect and on the intensity of the effect evoked by a fixed dose. Injections of PGE1 into a sensitive site typically produced a rapidly developing, short lasting, monophasic rise in body temperature. Saline injected at these sites produced no initial hyperthermia. Almost all of the active sites were located within the anterior hypothalamic/preoptic region (AH/PO). The sites of greatest reactivity were found in the ventral aspect of the tissue lying between the anterior commissure and the optic chiasm. These data suggest that the AH/PO region is an important and probably the only supramedullary site of PGE1 action in the rat brain.

Animals↗
PubMed1977

Hyperthermic effects of morphine: set point manipulation by a direct spinal action.

U Rats were implanted with chronic indwelling catheters in the lumbar spinal subarachnoid space in order to study the effects of morphine on body temperature. 2 Morphine administered intrathecally produced a dose-dependent rise in body temperature that was antagonized by naloxone. 3 The rise in body temperature evoked by a given dose of morphine appeared to be independent of the environmental temperture ((4 degrees C to 32 degrees C) and was consistently associated with coordinated thermoregulatory responses (i.e. shivering and tail vasoconstriction). The fall in body temperature observed in these hyperthermic animals, following naloxone, was associated with a vasodilatation which coincided with the fall to the premorphine temperature level. 4 Morphine administered systemically also produced hyperthermia. This was only partially reversed by intrathecal naloxone. In animals made tolerant to the hyperthermic effects of systemic morphine, the intrathecal administration of naloxone produced a fall in body temperature. 5 Naloxone alone, administered either intrathecally or systemically, had no effect upon body temperature. 6 We suggest that morphine exerts a direct, pharmacologically specific effect on the spinal cord, which results in an altered thermoregulatory set point in the rat.

Animals↗
PubMed1977

Antagonism by indomethacin of neurogenic hyperthermia produced by unilateral puncture of the anterior hypothalamic/preoptic region.

1. In unanaesthetized rats, restrained at an ambient temperature of 24 degrees C, the anterior hypothalamic/preoptic (AH/PO) region was lesioned unilaterally by acute mechanical puncture.2. In control (no pre-treatment) rats, unilateral AH/PO puncture produced a neurogenic hyperthermia which began immediately, reached its peak magnitude (mean peak magnitude = +2.3 degrees C) within 60-90 min and persisted usually for 8-16 hr. At defervescence, core temperature fell to a level near that of the pre-lesioning base line.3. The prostaglandin synthesis inhibitor, indomethacin, administered I.P. at doses of 5 and 15 mg/kg 1 hr before puncture of the AH/PO region, attenuated the lesion-induced hyperthermia in a dose dependent fashion. The higher dose reduced peak magnitude by 80% and the 6 hr Fever Index by 88%. The vehicle used to dissolve the indomethacin (60% DMSO/40% saline) did not significantly attenuate the hyperthermia.4. In rats that were hyperthermic after AH/PO damage, indomethacin (10-15 mg/kg I.P.) caused core temperature to fall promptly to near the prelesion base line. Reversal occurred whether the indomethacin was injected while core temperature was still rising or late in the plateau phase of the hyperthermia.5. It is suggested that the neurogenic hyperthermia elicited by unilateral lesioning of the AH/PO region was mediated by prostaglandins released from injured tissue and possibly from extravasated blood. Evidence is cited indicating that the most likely sites of action of the released prostaglandins are the surviving portion of the AH/PO region on the punctured side and the intact contralateral AH/PO region.

Animals↗
PubMed1976

Systematic examination in the rat of brain sites sensitive to the direct application of morphine: observation of differential effects within the periaqueductal gray.

An extensive mapping of the rat brain (403 sites) ranging from AP +8 to AP -3 revealed that the region showing maximum sensitivity to the intracerebral administration of morphine in the elevation of the nociceptive threshold lay within the periaqueductal gray. Analysis of the distribution of responsive sites indicated that the most active sites, those having the shortest latency of effect, were located within the ventrolateral aspect of the caudal periaqueductal gray. These antinociceptive actions of morphine were observed to be both dose-dependent and reversible by the administration of naloxone. We observed that microinjections of morphine could produce changes in the pinch withdrawal response which were distributed in a crude somatotopic fashion. Injections into the rostral aspect of the periaqueductal gray yielded a block of the pinch response in the rostral portions of the body, whereas such injections into the caudal periaqueductal gray always yielded a whole body analgesia. In the rostral sites, transient ipsilateral blocks of the pinch response were occasionally seen. A pinch block limited to the hind paws alone was never observed. It is suggested that morphine acting through the periaqueductal gray may actuate a potent supraspinal modulatory system related to the transmission of information derived from behaviorally aversive stimuli.

Animals↗
PubMed1976

Analgesia mediated by a direct spinal action of narcotics.

Narcotic analgetics administered directly into the spinal subarachnoid space of the rat via a chronically inserted catheter produce a potent analgesia that can be antagonized by naloxone. The narcotics, acting only at the spinal level, changed cord function to block not only spinal reflexes but also the operant response to painful stimuli.

Analgesia↗
PubMed1976

Chronic catheterization of the spinal subarachnoid space.

To administer drugs into the spinal subarachnoid space of unanesthetized and intact rats and rabbits, a procedure is described whereby a polyethylene catheter (PE-10) may be inserted through a puncture of the atlanto-occipital membrane and secured to the skull. Calibration experiments carried out with bromophenol blue dye, 3H-naloxone and 14C-urea revealed first, that there was little rostro-caudal diffusion of the injectate along the spinal axis and secondly, that even for compounds such as naloxone which can rapidly permeate neural tissues, the levels which do appear in the brain are small following the spinal subarachnoid administration of the drug. Control injections, administered either acutely or repeatedly over a prolonged period of time, had no detectable effect on the animal's behavior. These observations, as well as the lack of pathology in the spinal cords of rats having such catheters for periods of up to 4 months suggests that the implant is well tolerated.

Animals↗
PubMed1975

Effect of central cholinergic blockade on the hyperthermia evoked by prostaglandin E1 injected into the rostral hypothalamus of the rat.

The possibility of a cholinergic involvement in the hyperthermic action produced by the injection of prostaglandin E1 (PGE1) into the anterior hypothalamic/preoptic region of the rat brain was examined. Intracerebral injection of either atropine or mecamylamine prior to the injection of PGE1 failed to attenuate the PGE1-induced hyperthermia. Both atropine and mecamylamine by themselves produced a rise in colonic temperature. It thus seems unlikely that PGE1 evokes hyperthermia in the rat by releasing endogenous acetylcholine at muscarinic or nicotinic synapses in the rostral hypothalamus. The possibility that PGE1 acts by inhibiting the release of acetylcholine within this region requires additional investigation.

Animals↗
PubMed1975

The involvement of methysergide-sensitive receptors and prostaglandins in the hyperthermia evoked by 5-HT in the cat.

In the unanesthetized cat, an injection of 0.01 or 0.03 M 5-hydroxytryptamine into the rostral hypothalamus produced an immediate, short-lasting increase or decrease in body temperature. A delayed and long-lasting hyperthermia often followed the initial response. When indomethacin, 10 mg/kg, was administered intraperitoneally 3 hours prior to an injection of 5-hydroxytryptamine at sites which produced an initial increase in body temperature, the secondary hyperthermia was reduced or abolished but the immediate response remained undiminished. Pretreatment with methysergide, 2 mg/kg i.p., attenuated or abolished the initial temperature increase but did not reduce the delayed hyperthermia. The results suggest that the initial rise in body temperature produced by 5-hydroxytryptamine is mediated by activation of methysergide-sensitive 5-HT receptors and that the response is independent of prostaglandin release. The secondary hyperthermia, on the other hand, is apparently mediated by a sustained release of prostaglandins.

Analysis of Variance↗