pituitrin and Morphine-Dependence

The neurohypophyseal hormones oxytocin and vasopressin cause a variety of biological effects in animals which are mediated by central nervous system mechanisms. Among the best studied of these effects is the modulation of both memory processes and the development of drug tolerance and dependence. Neurohypophyseal hormones have also been shown to alter various physiological parameters such as heart rate and body temperature following central administration. In addition, these peptides can profoundly alter spontaneous, unlearned behavior in several rodent species. Many of the centrally mediated effects of neurohypophyseal hormones have been shown to be elicited at sites within the brain stem and the limbic system where vasopressin and oxytocin occur in cell bodies, axons and nerve terminals, suggesting a physiological role for these peptide effects. The various central effects of neurohypophyseal hormones involve different mechanisms which can be distinguished from one another on the basis of required dose, time-course of action, and structure-activity relationships. Thus, alterations of spontaneous behavior are mediated by putative receptors closely related to vasopressin receptors in blood vessels responsible for the peripheral pressor response while the effects on memory processes are mediated by a mechanism which is not closely related to those involved in the peripheral hormonal effects of the peptides. The influence of neurohypophyseal hormones on memory and attention may be useful clinically. A potential role for these peptides in mental disorders is discussed.

Topics: Animals; Autonomic Nervous System; Behavior, Animal; Brain; Cerebrovascular Circulation; Drug Tolerance; Humans; Intracranial Pressure; Mental Disorders; Mental Recall; Morphine Dependence; Oxytocin; Substance Withdrawal Syndrome; Vasopressins; Water-Electrolyte Balance

Topics: Alcoholism; Animals; Barbiturates; Drug Tolerance; Ethanol; Humans; Morphine; Morphine Dependence; Narcotics; Neurophysins; Oxytocin; Peptides; Pituitary Hormones, Posterior; Psychotropic Drugs; Substance-Related Disorders; Vasopressins

The neurohypophyseal hormones vasopressin and oxytocin modulate memory processes. Vasopressin facilitates, while oxytocin attenuates memory consolidation and retrieval. These influences are located in different regions of the molecules. Thus, the neurohypophyseal hormones act as precursor molecules for neuropeptides involved in memory processes. The covalent ring structures of both vasopressin and oxytocin mainly affect consolidation; the linear parts, retrieval processes; while nearly the whole oxytocin or vasotocin molecule is needed for attenuation of consolidation and retrieval. Regional studies, utilizing microdissection techniques in combination with a sensitive radioenzymatic catecholamine assay, revealed a distinct pattern of effects on cerebral alpha-methyl-p-tyrosine methylester-induced catecholamine disappearance following intraventricular vasopressin administration in limbic midbrain structures. In situations in which the amount of bioavailable vasopressin in the brain is absent, as is the case in the Brattleboro rat with hereditary diabetes insipidus, or neutralized in normal Wistar rats following the intraventricular administration of antivasopressin serum, regional catecholamine disappearance in most cases is altered in a direction opposite to that observed after intracerebroventricular vasopressin administration. These results indicate that vasopressin modulates memory processes by modulation of neurotransmission in distinct catecholamine systems. Recent experiments suggest that the influence of vasopressin on memory consolidation is mediated by the dorsal noradrenergic bundle via terminal regions of this bundle.

Topics: Amnesia; Animals; Biological Availability; Brain; Catecholamines; Chemical Phenomena; Chemistry; Drug Tolerance; Heroin Dependence; Humans; Melanocyte-Stimulating Hormones; Memory; Morphine Dependence; Oxytocin; Pituitary Gland, Posterior; Rats; Vasopressins

Morphine withdrawal is characterized by an increase in the hypothalamus-pituitary-adrenocortical (HPA) axis activity. Here, by means of in situ hybridization, the changes in CRH and vasopressin (AVP) mRNAs have been analysed within the rat hypothalamic paraventricular nucleus (PVN) during morphine dependence and after naloxone-precipitated morphine withdrawal. CRH and AVP mRNA expression were analysed 30 min following administration of saline or naloxone to control groups and to morphine dependent rats. The data for in situ hybridization analysis of PVN neurons show that there were no changes in the total size of labelled area for CRH or AVP mRNA during morphine withdrawal, indicating that dependence on morphine does not involve alterations in the number of neurons expressing CRH or AVP mRNA. However, levels of mRNA encoding for CRH were decreased in the PVN during morphine dependence and withdrawal. By contrast, injection of saline or naloxone to morphine dependent rats did not affect the intensity of AVM mRNA expression. All these findings are discussed in term of cellular events that couple morphine dependence-increased HPA axis activity with changes in gene expression in selective neurons of the PVN.

Topics: Adrenocorticotropic Hormone; Animals; Hypothalamo-Hypophyseal System; In Situ Hybridization; Male; Morphine Dependence; Naloxone; Narcotic Antagonists; Paraventricular Hypothalamic Nucleus; Pituitary-Adrenal System; Rats; Rats, Sprague-Dawley; RNA, Messenger; Substance Withdrawal Syndrome; Vasopressins

1. The present study investigated the mechanisms by which endogenous opioids regulate oxytocin secretion at the level of the posterior pituitary gland. Effects of the selective kappa-agonist U50,488 on oxytocin secretion were studied in urethane-anaesthetized lactating rats. Oxytocin secretion in response to electrical stimulation (0.5 mA, matched biphasic 1 ms pulses, 50 Hz, 60-180 pulses) of the neurohypophysial stalk was bioassayed on-line by measuring increases in intramammary pressure, calibrated with exogenous oxytocin. Intravenous (I.V.) U50,488 inhibited electrically stimulated oxytocin secretion, without affecting mammary gland sensitivity to oxytocin. The inhibition was dose related, with an ID50 of 441 (+194, -136) micrograms/kg and was naloxone reversible. Antagonism of endogenous beta-adrenoceptor activation by propranolol (1 mg/kg) reduced the potency of U50,488. The selective mu-agonist morphine (up to 5 mg/kg), had no effect on electrically stimulated oxytocin secretion, but depressed the mammary response to oxytocin. 2. In lactating rats given intracerebroventricular (I.C.V.) morphine infusion for 5 days to induce tolerance and dependence, I.V. U50,488 still inhibited electrically stimulated oxytocin secretion, but the ID50 was reduced to 170 (+78, -54) micrograms/kg; thus at the posterior pituitary the sensitivity of kappa-receptors is enhanced rather than reduced in morphine-tolerant rats, indicating the absence of cross-tolerance. In these rats, naloxone produced a large, sustained, fluctuating increase in intramammary pressure indicating morphine-withdrawal excitation of oxytocin secretion; I.V. U50,488 diminished this response, confirmed by radioimmunoassay, demonstrating the independence of mu- and kappa-receptors regulating oxytocin secretion. 3. In pregnant rats, I.C.V. infusion of morphine from day 17-18 of pregnancy delayed the start of parturition by 4 h, but did not significantly affect the progress of parturition once established, indicating tolerance to the inhibitory actions of morphine on oxytocin secretion in parturition, and lack of cross-tolerance to endogenous opioids restraining oxytocin in parturition. 4. Neurointermediate lobes from control and I.C.V. morphine-infused virgin rats were impaled on electrodes and perifused in vitro. Vasopressin and oxytocin release from the glands was measured by radioimmunoassay. Each gland was exposed to two periods of electrical stimulation (13 Hz, for 3 min). Naloxone (5 x 10(-6) M

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Biological Assay; Drug Tolerance; Electric Stimulation; Female; Injections, Intraventricular; Labor, Obstetric; Lactation; Morphine; Morphine Dependence; Naloxone; Oxytocin; Pituitary Gland, Posterior; Pregnancy; Propranolol; Pyrrolidines; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Vasopressins

Topics: Animals; Creatinine; Diuresis; Diuretics; Drug Interactions; Drug Tolerance; Electrolytes; Female; Humans; Male; Morphine; Morphine Dependence; Naloxone; Rats; Urine; Vasopressins

Topics: Animals; Arginine Vasopressin; Humans; Morphine Dependence; Naloxone; Oxytocin; Peptides; Rats; Vasopressins

Topics: Analgesia; Animals; Arginine Vasopressin; Body Temperature; Body Weight; Drug Synergism; Female; Humans; Morphine Dependence; Naloxone; Oligopeptides; Oxytocin; Rats; Structure-Activity Relationship; Vasopressins