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H J Haigler

Publications and source records attributed to H J Haigler.

36 records · Page 2Linked to original sources
PubMed1981

Methionine-enkephalin and morphine: amount ejected microiontophoretically.

The microiontophoretic transport numbers of Met-enkephalin and morphine were determined by ejecting the tritiated compounds from both 5-barrel and 7-barrel micro-pipettes into a small volume of 0.9% NaCl, using a series of ejection currents and various timed durations. The transport number of Met-enkephalin was 2-4 times less than that for morphine in 5- and 7-barrel pipettes. The transport numbers of both drugs in 5-barrel pipettes were significantly greater than those in 7-barrel pipettes. These results indicate the need for caution in comparing the data derived from different studies that use microiontophoresis. The transport numbers for morphine and Met-enkephalin were used to compare the effects of these agents on neuronal firing.

Animals↗
PubMed1981

Cyclic AMP, morphine, met-enkephalin and neuronal firing.

Extracellular recordings were made of spontaneous neuronal firing and of nociceptive stimulus-evoked neuronal firing in the mesencephalic reticular formation of the rat. Microiontophoretically administered morphine and met-enkephalin blocked the nociceptive stimulus-evoked neuronal firing of some neurons in the mesencephalic reticular formation; naloxone antagonized the effects of morphine and met-enkephalin. In neurons in which morphine and met-enkephalin blocked the nociceptive stimulus-evoked firing, the microiontophoretic administration of dibutyryl cyclic AMP (cAMP), 8-bromo cAMP and Ro 20,1724 (a phosphodiesterase inhibitor) consistently (96%) reversed this blockade of evoked firing. The effects of dibutyryl cAMP were specific, because butyrate and 5'-AMP, possible metabolites of the cAMP analog, reversed the blockade by morphine and met-enkephalin of the nociceptive stimulus-evoked neuronal firing much less frequently (29%). These result support the hypothesis that the occupation of opiate receptors triggers an inhibition of the enzyme, adenylate cyclase, as a mechanism of action. The cAMP analogs excited the spontaneous firing in only 60% of the neurons in which they reversed the opioid blockade of pain-evoked firing. This suggests that the mechanism of action of the cAMP analogs on spontaneous firing may differ from that on pain-evoked firing.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1980

Substance P, morphine and methionine-enkephalin: effects on spontaneous and evoked neuronal firing in the nucleus reticularis gigantocellularis of the rat.

A nociceptive stimulus (e.g., foot pinch) produced a significant increase in firing in cells in the nucleus reticularis gigantocellularis (NRGC) and surrounding areas of the rat brain. Substance P (SP), a putative nociceptive neurotransmitter, infrequently produced an increase in spontaneous neuronal firing when administered micro-iontophoretically to these areas. These data indicate that the NRGC is an area involved in nociception. However, SP does not appear to be the primary nociceptive neurotransmitter or neuromodulator in the NRGC because SP did not mimic or enhance the response to the nociceptive stimulus. Morphine (MS) and methionine-enkephalin (ENK), administered microiontophoretically, rarely had any effect on spontaneous neuronal firing or rarely modified the increase in neuronal firing evoked by the nociceptive stimulus. For this reason, the NRGC is apparently not an area where MS and ENK act directly to produce analgesia.

Animals↗
PubMed1980

Morphine and methionine-enkephalin: different effects on spontaneous and evoked neuronal firing in the mesencephalic reticular formation of the rat.

The technique of microiontophoresis was used to determine the effects of morphine and methionine-enkephalin (met-enkephalin) on spontaneous neuronal firing and on firing evoked by a nociceptive stimulus (evoked firing). Morphine and metenkephalin produced one of the three following patterns of effects on single units in the mesencephalic reticular formation: 1) morphine but not met-enkephalin blocked evoked firing; 2) met-enkephalin but not morphine blocked evoked firing; and 3) both morphine and met-enkephalin blocked evoked firing. For neurons exhibiting each of these three patterns, the mean T100, a modification of the T50 which is analogous to a dose-response curve, correlated with the effects of the drugs on evoked firing. There appear to be differences in cell size and location which are associated with different effects of the drugs. The difference in the effects of the drugs on evoked firing cannot be explained by differences in transport number, diffusion or degradation of the drugs, nor by different locations of the drug ejection barrels. Naloxone, administered intravenously or micriontophoretically, antagonized the drug-induced blockade. The effects of morphine and met-enkephalin on spontaneous firing did not correlate with their effect on evoked firing. Furthermore, in the majority of cases, the effects of morphine and met-enkephalin on spontaneous firing were not the same. These data indicate that there may be more than one type of opiate receptor in the mesencephalic reticular formation.

Action Potentials↗
PubMed1979

Drugs that antagonize limb flick behavior induced by D-lysergic acid diethylamide (LSD) in cats.

In cats observed in their home cages limb flicks (LF) are a sensitive measure of the behavioral effects of LSD. LF induced by LSD (50 microgram/kg) were blocked by dextrorphan (0.6 mg/kg), dextromethorphan (0.6 mg/kg), and imipramine (5 mg/kg) at doses that did not produce ataxia or sleep. Levorphanol (0.6 mg/kg), a narcotic that is a congener of dextrorphan, did not block LF induced by LSD possibly because it produced an excitatory effect when given alone. Pentobarbital at low doses (2 and 4 mg/kg) increased the number of LF induced by LSD but at a high dose (8 mg/kg) decreased LF induced by LSD either by producing ataxia, so the cats tended to remain immobile, or by producing sleep. Chlorpromazine (CPZ) at three doses (2, 4, and 8 mg/kg) attenuated the effects of LSD on LF, but did not block LF as completely as the above three blocking drugs, and produced ataxia and sleep.

Animals↗
PubMed1978

Morphine: effects on serotonergic neurons and neurons in areas with a serotonergic input.

The hypothesis that morphine acts on the serotonergic system to produce analgesia is based on the previous observations that (1) lesions and stimulation of midbrain raphe nuclei after the threshold to nociceptive stimuli; (2) morphine alters the turnover of serotonin (5-hydroxytryptamine; 5-HT). Microiontophoretic experiments were carried out to determine if morphine affected the firing rate of cells in five areas of the serotonergic system consisting of 5-HT containing neurons in the midbrain raphe nuclei (dorsal raphe and median raphe) or neurons in three areas (amygdala, optic tectum and subiculum) which are thought to receive a 5-HT input from the raphe nuclei. Morphine administered microiontophoretically slowed or inhibited the spontaneous neuronal firing in 34% of the cells studied in both the pre- and post-synaptic areas; systemically administered morphine gave similar results. However, the inhibition of neuronal firing by morphine in the five areas of the serotonergic system studied was not a specific narcotic effect because (1) it was not stereospecific; and (2) it was rarely blocked by naloxone. The inhibitory effect of morphine does not appear to be related to the analgesic effects of morphine because neuronal firing in the midbrain raphe nuclei and three possible postsynaptic areas was rarely altered by a nociceptive stimulus. It is concluded that (1) the analgesic effect of morphine is not related to an effect on neurons in the midbrain raphe nuclei and three areas which receive an identified 5-HT input; and (2) the effect of morphine on neurons in these five areas of the serotonergic system is not a specific narcotic effect.

Animals↗
PubMedDate not supplied

Analgesia produced by direct injection of morphine into the mesencephalic reticular formation.

Morphine administered intracerebrally (IC) (10 micrograms as the base on each side) into the MRF produced a significant dose dependent elevation of nociceptive threshold (i.e., analgesia) on the tail flick test and hemostat pinch test. However, morphine IC at lower doses had no analgesic effect. After morphine was injected IC (10 micrograms, bilaterally) into the MRF, naloxone, a specific narcotic antagonist, administered either IC at the same site (15 micrograms, bilaterally) or subcutaneously (10 mg/kg), antagonized the antinociceptive effects of morphine. Thirty percent of the animals given bilateral microinjection of 10 micrograms of morphine displayed hyperreactivity to mild stimuli. This hyperreactivity was not attenuated by large IC or systemic doses of naloxone. It was concluded that the MRF is a site where morphine may act to produce analgesia by a specific narcotic mechanism of action.

Analgesia↗