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Y F Jacquet

Publications and source records attributed to Y F Jacquet.

At least 19 recordsLinked to original sources
PubMed1988

Excitatory amino acids: role in morphine excitation in rat periaqueductal gray.

Morphine was previously found to elicit an explosive excitatory behavior following its injection at a high dose in the rat periaqueductal gray (PAG). This non-naloxone reversible excitatory action of morphine was mimicked by the GABAA receptor antagonist, bicuculline, suggesting that morphine excitation was due in part to GABAA receptor blockade. In this paper, we report that injections of the excitatory amino acid (EAA) analogues, N-methyl-D-aspartate (NMDA), quisqualate (Q) or kainate (K) in the rat PAG resulted in similar (but not identical) behaviors. The excitatory actions of morphine or of NMDA (but not Q or K) were blocked or attenuated by the NMDA receptor antagonist, 2-amino-7-phosphonoheptanoate. These results show that both GABAA receptors as well as receptors for the EAAs may contribute to the excitatory actions of morphine in the PAG, and suggest that GABA may normally function to counterbalance a tonic excitatory influence of the EAAs.

2-Amino-5-phosphonovalerate↗
PubMed1988

The NMDA receptor: central role in pain inhibition in rat periaqueductal gray.

An injection of the excitatory amino acid analogue, N-methyl-D-aspartate (NMDA), in the rat periaqueductal gray resulted in potent analgesia. A prior injection of the NMDA antagonist, (-)-2-amino-7-phosphonoheptanoate (D-AP7), antagonized this action, indicating a receptor-mediated action. NMDA given with morphine potentiated the morphine analgesia while D-AP7 blocked morphine analgesia. These results delineate for the first time a functional role for the NMDA receptor in the control of pain in the mammalian central nervous system.

2-Amino-5-phosphonovalerate↗
PubMed1987

Non-stereospecific excitatory actions of morphine may be due to GABA-A receptor blockade.

An explosive motor behavior (EMB) similar to that seen following morphine injection into the rat periaqueductal gray (PAG) was observed following an injection of GABA-A receptor antagonists into the rat PAG. In general, the potencies of certain opiates and known GABA-A antagonists in producing EMB following their injections into the PAG paralleled their potencies as GABA antagonists in a radioreceptor assay. We suggest that one of the dual actions of morphine in the CNS may be GABA blockade.

Adrenocorticotropic Hormone↗
PubMed1984

'Dystonia'-like postural asymmetry after microinjection of ACTH N-terminal fragments but not after ACTH1-39 in rat brainstem suggests role of neuropeptide mutation in genetic movement disorder.

N-terminal fragments of adrenocorticotropin (ACTH) was reported to exert potent 'dystonia'-like effects on posture and locomotion following a unilateral microinjection into the rat brainstem. The high reliability of this phenomenon provided a suitable animal model for the study of these actions. The present structure-activity study showed that ACTH1-39, in contrast to its N-terminal fragments, did not have any 'dystonic' actions, however transient or slight. Thus, the folded conformation of [1-39] in vivo may prevent its N-terminal region from interacting with those CNS sites that trigger 'dystonic' actions. These results suggest that genetically-linked human dystonia may have originated in part as a consequence of a mutation in the processing of the ACTH molecule, resulting in an aberrantly-folded conformation that allows its N-terminal region to trigger the dystonic syndrome.

Adrenocorticotropic Hormone↗
PubMed1983

Met5-enkephalin: potent contraversive rotation after microinjection in rat substantia nigra.

This study reports a novel action of Met5-enkephalin in the rat substantia nigra, i.e. potent contraversive rotation that is dose-dependent, site-specific, mimicked by morphine and blocked by naloxone. These results suggest that this pentapeptide may play an important modulatory role in the control of movement in this region of the central nervous system. Alterations in endogenous Met-enkephalin levels in the substantia nigra may be a contributive factor in Parkinson's disease, a movement disorder related to neuropathology of the substantia nigra.

Animals↗
PubMed1982

Postural asymmetry and movement disorder after unilateral microinjection of adrenocorticotropin 1-24 in rat brainstem.

A unilateral microinjection of adrenocorticotropin 1-24 in the rat brainstem in the region of the locus ceruleus resulted in postural asymmetry and movement disorder that resembled human dystonia, the severity and duration (2 to 3 days) being dose-dependent. These results show for the first time that neuropeptides in the brainstem may modulate posture and movement, and they suggest that some forms of movement disorder such as dystonia may be due to a disordered regulation of postural and locomotor mechanisms by adrenocorticotropin 1-24.

Adrenocorticotropic Hormone↗
PubMed1982

Opposite temporal changes after a single central administration of B-endorphin: tolerance and sensitization.

Rats were given a single unilateral microinjection of B-endorphin in the periaqueductal gray, followed by a second microinjection of the same dose of B-endorphin in the same site a week later. A decrease in the analgesic action (i.e., tolerance) but an increase in the hyperthermic action (i.e., sensitization) was observed over this interval. These results suggest that different receptors may mediate these actions of B-endorphin. In addition, these results indicate the need for caution in repeated-measurements studies using this opiate peptide, since the assumption that such temporal effects dissipate within 3-5 days, with resulting minimal carry-over effects from the preceding treatment appears to be unjustified.

Analgesia↗
PubMed1982

Dual actions of morphine on the central nervous system: parallel actions of beta-endorphin and ACTH.

In the studies described above, the intracerebral microinjection technique was used to study the actions of morphine at morphine-sensitive sites, the periaqueductal gray (PAG) and the midbrain reticular formation (MRF). In the PAG, morphine exerted dual actions: inhibitory and excitatory. In the MRF, morphine exerted an excitatory action only, indicating that the dual actions of morphine are dissociable and site specific. Following microinjection into the PAG, beta-endorphin exerted an inhibitory, and ACTH an excitatory, action, i.e., each duplicated one of morphine's dual actions. These results indicated that receptors for the endogenously occurring peptides, beta-endorphin and ACTH, may play a role in morphine's potent pharmacological actions. Although these studies do not shed direct light on the physiological role of these neuropeptides and their receptors, nor on their potential roles in the functional regulation of brain (especially in diseased mental states), it may be permissible to offer some speculations. We previously proposed that beta-endorphin may be an endogenous antipsychotogen, and that a deficiency in brain beta-endorphin may underlie some forms of psychopathology. In view of beta-endorphin's biosynthetic link to ACTH, and the behavioral effects of beta-endorphin (sedated immobility) that was found to be opposite in kind to those of ACTH (fearful hyperreactivity) following administration into brain, it is possible that these two neuropeptides may have regulatory roles in maintaining a functional balance in brain. (It may be speculated that these biosynthetically linked neuropeptides served survival functions of "flight" and "freeze" in our evolutionary ancestors.) An imbalance in the bioavailability of either of the two neuropeptides, e.g., a deficiency of beta-endorphin or an excess of ACTH (perhaps due to the lack of the specific enzymes that cleave these peptides from their parent prohormone) may be an etiological factor in some forms of chronic functional disorders of the brain.

Adrenocorticotropic Hormone↗
PubMed1981

Morphine and ACTH1-24: correlative behavioral excitations following micro-injections in rat periaqueductal gray.

Rats implanted with bilateral cannulas in the periaqueductal gray exhibited similar behavioral excitations following microinjections of morphine sulphate and ACTH1-24. Injections were more effective when the sites were located within rather than below the periaqueductal gray. Analgesia was observed following morphine but not ACTH microinjection. These results confirm that morphine exerts a dual action, inhibitory (i.e. analgesic) and excitatory, with ACTH mimicking only the latter action.

Adrenocorticotropic Hormone↗
PubMed1980

Excitatory and inhibitory effects of opiates in the rat vas deferens: a dual mechanism of opiate action.

Both natural (-)-morphine and its unnatural enantiomer (+)-morphine exert an excitatory action on electrically stimulated contractions of rat vas deferens. Preexposure to (-)-morphine results in cross-tolerance to the inhibitory action of beta-endorphin. (-)-Naloxone and its stereoisomer (+)-naloxone also exert an excitatory action, but only (-)-naloxone bocks the inhibtory action of beta-endorphin. Thus morphine exerts a dual action on a peripheral organ: one an inhibitory action mediated by the stereospecific endorphin receptor that is blocked stereospecifically by naloxone, the other an excitatory action mediated by a nonstereospecific receptor that is not blocked by naloxone. The opiate abstinence syndrome is seen as due to the unmasking of the excitatory action of opiates when its concomitant inhibitory influence is removed by selective blockade by naloxone or weakened by selective tolerance. The view that the rat vas deferens is devoid of morphine receptors is now seen as arising from a reverse example of morphine's dual action: the masking of the inhibitory action of morphine by its concomitant and more potent excitatory action.

Animals↗
PubMed1980

Stereospecific, dose-dependent antagonism by naloxone of non-opiate behavior in mice.

When mice were placed in a novel environment, they exhibited behavioral activation, characterized by a high frequency of jumps, rearings, groomings, digging, etc. Naloxone exerted a dose-dependent antagonism of this behavior. The antagonism was stereospecfic, with the enantiomer, (+)-naloxone failing to antagonize this behavior. Morphine-injected mice showed a different behavioral syndrome, i.e., Straub tail and a compulsive, robot-like ambutation around the perimeter of the bin, with a total absence of jumps, rearings, etc. The morphine behavioral syndrome was antagonized by naloxone at 1 mg/kg, while higher naloxone doses were required to antagonize the behavioral activation in a novel environment. These results suggest that stereospecific antagonism by naloxone is a necessary but not sufficient condition for defining opiate-like action.

Animals↗
PubMed1978

Opiate effects after adrenocorticotropin or beta-endorphin injection in the periaqueductal gray matter of rats.

Injections of adrenocorticotropic hormone (ACTH) into the periaqueductal gray matter of drug-naive rats resulted in a dose-dependent opiate abstinence syndrome characterized by fearful hyperreactivity and explosive motor behavior. Injecting shorter chains of ACTH caused attenuated forms of this behavior. Injections of beta-endorphin at this same site caused opposite behavior: sedative, analgestic, and catatonic. If the effects of morphine are mediated by two classes of receptor) and the other which is not stereospecific and naloxone-insensitive--the endogtor)--and the other which is not stereospecific and naloxone-insensitive the endogenous ligand of the second receptor may be ACTH. The neuropeptides ACTH and endorphin may be part of an integrated neuromodulatory system, and the opiate abstinence syndrome may be the result of an altered interaction between the two receptor systems.

Adrenocorticotropic Hormone↗
PubMed1977

Stereospecific and nonstereospecific effects of (+)- and (-)-morphine: evidence for a new class of receptors?

The unnatural (+) enantiomer of morphine had minimal activity in three opiate assays in vitro: the rat brain homogenate binding assay, the electrically stimulated guinea pig ileum assay, and the inhibition of adenylate cyclase in neuroblastoma X glioma hybrid cell homogenates. When (+)-morphine was microinfected into the periaqueductal gray (a site known to mediate morphine analgesia) of drug-naive rats, there was only minimal analgesia, but the hyperresponsivity usually observed after microinfection of (-)-morphine occurred. Also, when (+)-morphine was microinfected into the midbrain reticular formation of drug-naive rats, rotation similar to that following microinjection of (-)-morphine occurred. These behaviors were not blocked by naloxone. Significantly, they typically occur in precipitated abstinence in morphine-dependent rats. These observations suggest that there are at least two classes of receptors, one stereospecific and blocked by naloxone and the other only weakly stereospecific and not blocked by naloxone, and that precipitated abstinence may be due, in part, to a selective blockade of receptors of the former class but not of the latter.

Adenylyl Cyclase Inhibitors↗