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Biomedical subjects

W T Chance

Publications and source records attributed to W T Chance.

At least 91 records · Page 5Linked to original sources
PubMed1982

Delay of cancer anorexia following intraventricular injection of para-chlorophenylalanine.

Serotonergic mediation of cancer anorexia was investigated in immature female rats following the intraventricular injection of para-chlorophenylalanine (PCPA) or normal saline. Significant anorexia developed 6 days after the induction (IM) of Walker 256 carcinosarcomas in saline-treated rats. Although tumor-bearing rats treated with PCPA ate less than PCPA-injected controls by day 7, their feeding response was significantly greater than that of saline-treated tumor-bearing rats on days 5, 6 and 7. The PCPA treatment had no significant effect on food intake in nontumor-bearing rats. Biochemical analysis revealed significant elevations in plasma free tryptophan, brain tryptophan and brain 5-hydroxyindoleacetic acid in saline-treated tumor-bearing rats. Brain serotonin, 5-hydroxyindoleacetic acid and norepinephrine levels were decreased in PCPA-treated rats. Although these data may provide some support for a serotonergic mediation of cancer anorexia, additional mechanisms are clearly indicated.

Animals↗
PubMed1982

Analysis of brain indoleamines and catecholamines associated with burn-induced anorexia.

Guinea pigs subjected to a full-thickness 30% body surface flame burn significantly reduced food intake and lost weight for 5 days thereafter. Comparison of brain monoamine changes in burned, pair-fed control, and freely feeding control groups revealed normal levels of norepinephrine and elevated concentrations of dopamine in burned animals compared to the pair-fed control group. Levels of the serotonin precursor, tryptophan, and metabolite, 5-hydroxyindoleacetic acid, were also increased in burned compared to pair-fed animals, suggesting increased activity of indoleamine neurons. Although brain catecholamine levels were not correlated with food intake, significant negative correlations between food consumption and tryptophan, serotonin, and 5-hydroxyindoleacetic acid were observed. These data suggest that aberrations in indoleamine and possible catecholamine neurotransmitter systems may be involved in the mediation of burn-induced anorexia.

Amino Acids↗
PubMed1980

Autoanalgesia: opiate and non-opiate mechanisms.

Autoanalgesia (behaviorally-activated antinociception) was elicited by lesion-induced hyperemotionality or the classical conditioning of fear to the environmental stimuli associated with measuring antinociception. Both hyperemotionality and antinociception exhibited parallel decline in septal-lesioned rats with daily handling and in VMH-lesioned rats following treatment with diazepam. Autoanalgesia elicited by conditioned fear was blocked by spinal cord transection but not by diazepam. Although opiate binding experiments suggested the involvement of endorphins as mediators of autoanalgesia, hypophysectomy, morphine tolerance or very high doses of opiate antagonists failed to reduce the antinociception. Electrolytic lesions of the nucleus raphe magnus, a descending serotonergic system, did cause a significant reduction in autoanalgesia. Therefore, endorphin systems may be activated by the stress involved in autoanalgesic paradigms as a parallel system, whose functional integrity is not necessary for the expression of behaviorally-induced antinociception.

Animals↗
PubMed1979

Non-specificity of "behavioral despair" as an animal model of depression.

When mice are forced to swim in a restricted space, they will cease attempts to escape and adopt a characteristic immobile posture which can be readily identified and timed. Imipramine decreased the duration of immobility in a 4 min swimming test in a dose-related manner. Likewise, caffeine, triiodothyronine and pentobarbital reduced immobility. These latter findings shed doubt upon the specificity of the behavioral despair swimming test to identify substances with antidepressant activity.

Animals↗
PubMed1979

Autoanalgesia: acquisition, blockade and relationship to opiate binding.

Acquisition of autoanalgesia (behaviorally activated antinociception) was assessed across 7 consecutive days by shocking rats 10 sec after the determination of their tail-flick latencies. Thus the effect of conditioned fear on antinociception was being investigated, since each shock preceded the subsequent tail-flick test by 24 h. Autoanalgesia was acquired by the second fear-conditioning trial. Although pretreatment with naltrexone or diazepam had no effect, spinal cord transection at the thoracic level effectively obviated autoanalgesia. Investigations of opiate and opioid binding indicated significantly less binding in the fear-conditioned rats as well as an inverse relationship between binding and antinociception. These changes in binding are suggestive of partial mediation of autoanalgesia by an endogenous opiate peptide that is released by the fear-conditioning procedure.

Analgesia↗
PubMed1979

Lack of cross-tolerance between morphine and autoanalgesia.

The acquisition of autoanalgesia (behaviorally-induced antinociception) was investigated in morphine-tolerant and non-tolerant rats. Tolerance to morphine did not affect analgesia acutely-elicited by a brief (15 sec) schedule of footshock. Similarly, analgesia elicited by classically conditioned fear wasnot attenuated by morphine tolerance. These data suggest that endorphins may not be the principle mediators of autoanalgesic phenomena.

Analgesia↗
PubMed1979

Lack of effect of naloxone on autoanalgesia.

Autoanalgesia (behaviorally-induced antinociception) may be elicited by acute stress or clasically conditioned fear. Antinociception within both of these paradigms is reportedly associated with increased CNS opioid peptide activity. Large doses of naloxone (20 mg/kg) failed to modify antinociception elicited by acute footshock or conditioned fear in rats. Naloxone (4 mg/kg) was also ineffective against antinociception following footshock in mice. These data suggest that if an endorphin does mediate autoanalgesia, the affinity of its receptor for naloxone is very low. Alternatively, parallel opioid and non-opioid systems may be activated by autoanalgesic procedures, with antagonism of the opioid component being insufficient to reduce the antinociception.

Analgesia↗
PubMed1979

Effect of autoanalgesia on CNS enkephalin receptors.

Fear conditioning to foot shock (15 sec/day, 12 days) elicited autoanalgesia in 10 male (Sprague-Dawley) rats, while 17 non-shock control rats exhibited no analgesia as measured by the tail-flick assay. The binding of 3H-leu-enkephalin to synaptosomal preparations isolated from fear conditioned (experimental) and control animals was analyzed. At leu-enkephalin concentrations of 10(-9) M or less, both synaptosomal preparations demonstrated high affinity binding with dissociation constants on the order of 10(-10). Binding of leu-enkephalin could not be displaced by a hundred-fold excess of naloxone at leu-enkephalin concentrations less than 10(-9) M. However, the ability of naloxone to compete with leu-enkephalin for binding sites progressively increased at concentrations greater than 10(-9) M leu-enkephalin. At these ligand concentrations, the competition of naloxone for leu-enkephalin binding sites was more dramatic in the control than in the experimental animals. These data support the existence of two classes of receptors for leu-enkephalin, one of which is not blocked by opiate antagonists. Furthermore, changes in binding capacity associated with autoanalgesia produced by conditioned fear are consistent with the hypothesis of endogenous release of opiate-like peptides in response to stress.

Analgesia↗
PubMed1979

Morphine-induced behavioral disruption in rats chronically depleted of brain dopamine.

The ability of rats, chronically depleted of brain dopamine (DA), to develop tolerance to morphine (120 mg/kg, s.c.) given twice daily was studied using a food-reinforced operant procedure (FR-10). DA was depleted via the administration of 6-OHDA (150 ug, ict.) and desmethylimipramine (DMI; 25 mg/kg, ip.) to rats 14 days of age. This procedure resulted in a 61% depletion of brain DA when these rats were 120 days of age, while norepinephrine levels were not significantly affected. The response rates of DA-depleted and vehicle (ict.) + DMI treated controls were equally suppressed by various acute doses of morphine, but the DA-depleted group appeared to develop tolerance to the higher morphine dosage regimen (120 mg/kg, b.i.d) faster than the control group. In addition, DA-depleted rats exhibited a greater suppression of response rates 24 hr after the cessation of morphine treatment.

Animals↗
PubMed1978

Effects of medial raphe and raphe magnus lesions on the analgesic activity of morphine and methadone.

The effects of lesions of the raphe nuclei on opiate-induced antinociception and brain serotonin (5-HT) levels were investigated. Lesions of the medial raphe nucleus effectively antagonized the analgesic effects of morphine, but not methadone, and lowered brain 5-HT. The decrement in analgesic activity of morphine was reversed by pretreatment with 5-hydroxytryptophan. Lesions of the raphe magnus, a descending 5-HT system, antagonized the analgesic potency of both morphine and methadone. These experiments indicate a differential effect of 5-HT manipulation on opiate-induced analgesia, suggesting a different mechanism of analgesic action for morphine and methadone.

Analgesics↗
PubMed1978

A comparison of nicotine and structurally related compounds as discriminative stimuli.

1 Of seven nicotine-like compounds tested as discriminative stimuli in the rat, only 3-pyridyl-methylpyrollidine (3-PMP) generalized to the stimulus effects of nicotine. 2 3-PMP caused equivalent nicotine-like responding at a dose (800 microgram/kg) approximately 4 times that used for the original nicotine discrimination (200 microgram/kg). The ED50 for 3-PMP was about 5 times that for nicotine. 3 Testing of the compounds as possible antagonists of the nicotine-elicited cue were negative. 4 The nicotine-like cue produced by an 800 microgram/kg injection of 3-PMP was effectively blocked by mecamylamine but not by hexamethonium or atropine. Thus, 3-PMP appears to produce generalization to the nicotine cue via action on central nicotinic-cholinoceptors as has been previously reported for the nicotine discriminative stimulus. 5 Mecamylamine blocked the stimulus-effects of 3-PMP (800 microgram/kg) and of nicotine (200 microgram/kg) with an ED50 of 0.32 and 0.20 microgram/kg respectively.

Animals↗
PubMed1978

The discriminative stimulus properties of cyclazocine: generalization studies involving nalorphine, morphine and LSD.

Rats learned to discriminate cyclazocine (2 mg/kg, i.p.) from saline using a two-lever operant (FR-4) procedure within 10 sessions under each drug condition. The cyclazocine discriminative stimulus (DS) was both dose- and time-related, being antagonized by naloxone at doses approximately 80 times that necessary to block the discriminative stimulus effect of morphine. Cyclazocine also generalized to nalorphine, but not to morphine, pentazocine or LSD. These data suggest that cyclazocine produced DS control of behavior by acting at CNS sites different from those affected by morphine or LSD.

Animals↗