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A Pert

Publications and source records attributed to A Pert.

119 records · Page 7Linked to original sources
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Nigral 6-hydroxydopamine lesions equally decrease mu and delta opiate binding to striatal patches: further evidence for a conformationally malleable type 1 opiate receptor.

We have investigated the effect of nigral 6-hydroxydopamine (6-OHDA) lesions on binding of the mu receptor ligand dihydromorphine (DHM) and the delta receptor ligand [D-Ala2, D-Leu5]-enkephalin (DADLE) to sections of rat striatum under conditions which yield mu-like and delta-like ligand selectivities at discrete receptor patches (Type 1 receptor). 3H-DHM binding was decreased 43% while 3H-DADLE was decreased 22%. However, when the contribution of diffuse binding (Type 2) which is not affected by 6-OHDA is subtracted from the patch, the decrease is approximately 49% for both ligands. These data support the hypothesis that the Type 1 receptor of striatal patches is a conformationally malleable receptor entity which can exist in states having high affinities for various classes of opiate ligands.

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Localization of the antinociceptive action of morphine in primate brain.

Microinjections of morphine sulfate (20-40 mu g) were made into various subcortical regions of the rhesus monkey brain. The effects of these injections were evaluated on the nociceptive threshold as defined by the shock titration technique. The results of this preliminary investigation indicate that the region of maximal antinociceptive sensitivity to morphine in the primate is the periventricular-periaqueductal gray matter. It is tentatively suggested that morphine lowers that affective tone or the aversive component of pain by its action on the midbrain central gray and periventricular areas--both important projection and integration areas of the extralemniscal somatosensory system.

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Localization of cholecystokinin receptors in relation to the nigrostriatal and mesolimbic dopaminergic pathways.

The anatomical distribution of cholecystokinin (CCK)-dopamine (DA) neurons suggests that CCK could modulate dopaminergic activity. To further investigate that hypothesis, the cellular localization of CCK receptors was ascertained in relation to mesolimbic and nigrostriatal DA pathways after a series of chemical lesions induced with ibotenic acid and 6-hydroxydopamine. The results suggest that CCK receptors are not localized on dopaminergic neurons of the nigrostriatal and mesolimbic pathways.

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The actions of opiates in the rat substantia nigra: an electrophysiological analysis.

Single unit recording and micropressure ejection techniques were used to investigate the actions of opiates on dopaminergic and non-dopaminergic neurons in the rat substantia nigra. Systemic administration of morphine, 1 to 4 mg/kg, led to a naloxone-reversible increase in firing rate of all zona compacta dopaminergic (ZC) neurons examined (n = 10). In a specifically defined subpopulation of non-dopaminergic nigral zona reticulata (ZR) neurons, systemically administered morphine led to a naloxone reversible decrease in activity (n = 9). D-Ala2-d-leu5 (DADL)-enkephalin, when applied directly onto ZC neurons by micropressure ejection techniques, had no effect on their firing rate. In contrast, micropressure ejection of DADL enkephalin onto ZR neurons produced a decrease in firing rate which was blocked by systemically administered naloxone. Morphine sulfate applied by pressure ejection onto both ZC and ZR neurons produced mixed results which were not always blocked by naloxone. These results suggest that one of the mechanisms by which opiates increase dopaminergic neurotransmission is through disinhibition of dopaminergic neurons in the substantia nigra.

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Evidence for an endogenous peptide ligand for the phencyclidine receptor.

Porcine brain contained an active factor that competed with [3H]-phencyclidine (PCP) for binding to rat brain membranes. On reverse phase high pressure liquid chromatography, the active material eluted between 38-42% acetonitrile. Gel filtration chromatography of the factor predicted a molecular weight of approximately 3000 daltons. The endogenous substance appeared to be selective for PCP receptors as it did not interact with either benzodiazepine, neurotensin, nor with mu, delta, or kappa opioid receptors. The active material showed a heterogenous distribution in brain, with highest concentrations found in hippocampus and cortex. It is likely to be a small peptide since various proteases eliminated or markedly reduced the potency of the compound in a [3H]-PCP binding assay. The material also possessed PCP-like activity in two bioassays. Like PCP, it induced contralateral rotational behavior after unilateral intranigral injection and depressed spontaneous cell activity after iontophoretic micropressure application in hippocampus and cerebral cortex. Thus, this small peptide is likely to be an endogenous ligand for the PCP receptor.

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Enhanced corticosterone release after a modified forced swim test in Fawn hooded rats is independent of rearing experience.

Recent findings have demonstrated that Fawn hooded (FH/Har) rats exhibit enhanced plasma corticosterone (CORT) responses compared to Wistar rats after exposure to an open field, whereas this effect was not influenced by early social experience. In contrast, it was found that behavior in a modified version of the Porsolt Forced Swim Test (Porsolt FST) was affected by both strain and social experience. An important part of this study included modifications of the Porsolt FST that allowed separation of multiple behavioral endpoints. The present experiment was conducted to determine if FH/Har rats also exhibit enhanced CORT responses after exposure to the modified forced swim test, and whether CORT levels might predict the behavioral response in this context. After the initial exposure in the modified forced swim test FH/Har rats had higher CORT levels than Wistar rats, but this difference was not affected by isolation rearing. However, CORT levels were not correlated with the main behavioral measures assayed in this test. Nonetheless, the data confirm that FH/Har rats have altered HPA axis responses to stressors.

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Locomotor-stimulating effects of indirect dopamine agonists are attenuated in Fawn hooded rats independent of postweaning social experience.

The effects of the indirect dopamine (DA) agonists cocaine and D-amphetamine on locomotor activity were examined in Fawn hooded (FH) rats and Wistar rats. The effect of isolation rearing was also examined to determine if it might have different effects in these two strains. Contrary to previous findings in other rat strains, only small increases in locomotor-stimulating responses to low doses of cocaine were observed in the present study as a result of isolation rearing. However, at higher cocaine doses, locomotor activity was substantially attenuated in FH rats relative to Wistar rats. A similar pattern of effects was observed for amphetamine in FH rats but only at the intermediate dose. The effects of strain and rearing were independent. There was no evidence for interactions between these factors.

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