Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jun 1996
Supraspinal delta 2 opioid agonist analgesia in Swiss-Webster mice involves spinal GABAA receptors.
The tail-flick response is a spinal reflex that can be modulated by administration of antinociceptive agents supraspinally through activation of descending systems and involvement of the action of neurotransmitters in the spinal cord. Descending noradrenergic and serotonergic systems are involved in morphine (and other mu opioid receptor agonists)-induced antinociception. These descending systems, however, are not involved in supraspinal delta opioid receptor agonist-induced antinociception. ⋯ The intrathecal administration of 2-hydroxysaclofen, a GABAB receptor antagonist, had no effect. These studies suggest that supraspinal delta 2, like delta 1, opioid receptor action involves spinal GABAA receptors, but delta 2, unlike delta 1, action does not involve GABAB receptors. Thus, the supraspinal delta 1 agonist action (heroin, DPDPE) and the delta 2 agonist action (6MAM, DSLET) can be further differentiated by the selectivity of the spinal GABA receptors involved in Swiss-Webster mice.
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Pharmacol. Biochem. Behav. · May 1996
Effect of chronic mild stress on circadian rhythms in the locomotor activity in rats.
The purpose of this study was to assess whether the chronic mild stress (CMS) procedure, as a realistic animal model of depression, affects the rhythms of the locomotor activity in rats. Rhythm parameters (period, mesor, amplitude, acrophase, and percent rhythm) were estimated from the best-fitted cosine function curves. Period is the length, mesor is the mean level, amplitude (A) is the extent, acrophase is the timing of the rhythm; percent rhythm represents the variability estimated by the cosine regression and expressed as a percentage of the total variability of raw data. ⋯ In contrast to the results from LL, the cosine curves from DD were similarly shifted in relation to the subjective light-dark cycle. After a restoration of the LD cycle the levels of the 24-h activity of both groups became equal in the 13th week, but the light and dark phase differences between the groups were still statistically significant (p < 0.05). The present results indicate that CMS exerts distinct and prolonged disturbances of the diurnal and circadian rhythms of the locomotor activity in the rats.
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Pharmacol. Biochem. Behav. · May 1996
ReviewActivation of the HPA axis by immune insults: roles and interactions of cytokines, eicosanoids, glucocorticoids.
It is now well established that challenges to the immune system (e.g., infection, inflammation) initiate diverse changes in neuroendocrine function, the most overt of which is activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. The glucocorticoids that are released as a consequence fulfill a vital role in the maintenance of homeostasis that is effected in part through their ability to quench the immune/inflammatory response and thereby prevent them accelerating to a point where they become hazardous to the host. This article discusses the putative mechanisms by which immune insults stimulate the HPA axis, with particular reference to the roles and interactions of the interleukins, eicosanoids and glucocorticoids.
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Pharmacol. Biochem. Behav. · Mar 1996
3-O-acetylmorphine-6-O-sulfate: a potent, centrally acting morphine derivative.
In view of the potent analgesia exhibited by the apparent structurally dissimilar morphine-6-O-glucuronide (M6G) and morphine-6-O-sulfate (M6S) conjugates of morphine, we have examined the effect of structural modification of M6S on analgesic activity, using the tail-flick test. Changes in the M6S structure were made that would affect the lipophilicity and polarity of the molecule. Subcutaneous (sc) and intracerebroventricular (ICV) administration of equimolar doses of morphine, M6S, 3-O-acetylmorphine-6-O-sulfate (M3A6S), 3-O-benzoylmorphine-6-O-sulfate (M3B6S), and 3-O-acetyl-N-methylmorphinium-6-O-sulfate (MM3A6S) were employed. ⋯ In contrast, the nonanalgesic compounds M3B6S and MM3A6S showed weak receptor binding ability compared to morphine. These results indicate that lipophilicity alone is not a determinant of analgesic activity in these novel morphine derivatives. These modified effects of morphine by the conjugations at the 3- and 6-position, appear to be due to their altered interactions with opioid receptors.
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Pharmacol. Biochem. Behav. · Dec 1995
Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats.
Cocaine (5-40 mg/kg, intraperitoneally) enhanced locomotion and rearing accompanied with head circling and body shaking. Although at 40 mg/kg typical stereotypy licking occasionally appeared, 40% of the rats died. At doses that did not affect physiologic locomotion and rearing, the D1-receptor antagonist SCH23390 but not D2 antagonist raclopride inhibited locomotion and rearing stimulated by cocaine (20 mg/kg). ⋯ The increases of locomotion and rearing, head circling, and body shaking induced by cocaine may involve the indirect activation of postsynaptic D1 and D2 receptors, presumably via dopamine release, resulting from inhibition of the presynaptic D2 receptors. These results also provide evidence that the indirect stimulation of postsynaptic D2 receptors by cocaine (20 mg/kg) is insufficient to induce stereotyped behaviors, and that the role of dopamine D1 receptors in mediating the behavioral actions of acute cocaine appears to be more important than that of D2 receptors. Our results also suggest that bromocriptine may be useful for the treatment of acute cocaine poisoning.