1,721,014 research outputs found
Susceptibility to Psychiatric Diseases After Cannabis Abuse in Adolescence: Animal Models
No full textTherapeutic potential of cannabidivarin for epilepsy and autism spectrum disorder
No full textRecent years have seen a renewed interest on the possible therapeutic exploitations of specific cannabinoids derived from the Cannabis sativa plant. Thus far, the most studied non-psychotomimetic cannabinoid is cannabidiol (CBD), which has shown promising therapeutic potential for relieving a variety of neurological diseases. However, also its propyl analogue, cannabidivarin (CBDV), has recently gained much attention as a potential therapeutic agent for the management of disabling neurological conditions. This review aims at providing a comprehensive and updated overview of the available animal and human data, which have investigated the possible therapeutic potential of CBDV for the management of epilepsy and autism spectrum disorder
Influence of ω-conotoxin on morphine analgesia and withdrawal syndrome in rats
No full textThe effect of ω-conotoxin on opiate analgesia and withdrawal syndrome was investigated in rats. ω-Conotoxin given i.c.v. and i.p. caused weak analgesia in the tail-flick test. When the toxin (20 ng/rat) was given i.c.v. immediately before morphine (1.5 μg/rat i.c.v.) the resultant analgesic effect was additive. In contrast, the analgesia elicited by morphine (3 μg/rat i.c.v.) was greatly reduced after 24-h pretreatment with the toxin (20 ng/rat i.c.v.). The systemic administration of the toxin (10 μg/kg i.p.) did not affect morphine analgesia whether ω-conotoxin was coadministered with morphine (2.5 mg/kg i.p.) or was given 24 h before the opiate (5 mg/kg i.p.). ω-Conotoxin i.c.v. injected in morphine-dependent rats 15 min before naloxone challenge significantly attenuated the abstinence syndrome. On the contrary systemic administration of ω-conotoxin failed to suppress the morphine withdrawal syndrome. The present results suggest that ω-conotoxin affects both acute and chronic effects of morphine. © 1992
INTRAUTERINE POSITION HAS LONG-TERM EFFECTS ON M-OPIOID INDUCED BEHAVIOURS IN MICE
No full textIn multiparous rodents, a naturally occurring variation in degree of exposure to sex steroids during the prenatal phase of sexual differentiation derives from the in-utero proximity to opposite sex foetuses. So far, the studies on intrauterine position (IUP) phenomenon have mostly focused on traits relating to reproduction and behaviour, while its influence on neurochemical substrates and pharmacological response has been largely unexplored. We investigated possible variations in the function and the profile of expression of the p-opioid receptor system in three groups of adult mice from known IUP: 2M mice (located between two males), OM (between two females), and 1 M (between a male and a female). Autoradiographic study revealed in female mice that proximity to at least a male in utero (1M and 2M position) resulted associated at adulthood with an increased density of midbrain mu-opioid receptors. Behavioural observations were conducted following injection with the specific p-opioid agonist Fentanyl (at 0, 0.01 or 0.05 mg/kg IP). A drug-conditioned place preference test confirmed that 1M and 2M subjects were also more sensitive to the rewarding effects of the drug, since mice spent significantly more time in the drug-paired compartment than OM subjects. In a hotplate test, 2M subjects showed levels of drug-induced analgesia that were much higher than other IUP groups. No reliable differences were observed between the IUP groups for locomotor activity upon drug treatment. Overall, these data indicate for the first time that the organisation of the mu-opioid receptor system in the brain, as well as a differential vulnerability to abuse of opiate drugs can be modulated by epigenetic variables such as the prenatal in utero contiguity to male foetuses. (C) 2003 Elsevier Science Ltd. All rights reserved
Central pertussis toxin abolishes the intestinal inhibition induced by intracerebroventricular morphine
No full textMorphine Withdrawal Syndrome and G Protein Expression: a Study of the Time Course in the Rat Central Nervous System
No full textWe followed the changes in G protein α subunit expression and levels throughout the brain during the naltrexone‐precipitated withdrawal syndrome in morphine‐dependent rats. Intraperitoneally injected naltrexone (10 mg/kg) in rats made tolerant to morphine resulted in sustained withdrawal. Additional naltrexone doses 6, 24 and 72 h later still induced a significant abstinence syndrome. At the fifth naltrexone injection (8 days later) counted signs were completely resolved but checked ones were not. Besides the behavioural modifications, opiate withdrawal affected G protein expression in the central nervous system. In situ hybridization showed that Gαs and Gαo mRNA, whose levels are increased in tolerance, changed further during opiate withdrawal. Specifically, the αs mRNA in the hypothalamus was reduced after the first naltrexone injection and reached the control level with subsequent doses. However, αo mRNA expression in the olfactory system remained elevated after repeated naltrexone injections, declining to the control value only after the fifth dose. The amounts of Gαs and Gαo protein closely followed the time course of mRNA. The relationship between behavioural and biochemical parameters is discussed, together with the regional selectivity of the modifications. Copyright © 1995, Wiley Blackwell. All rights reserve
Modulation of extracellular signal-regulated kinases cascade by cronic Delta(99-tetrahydrocannabinol treatment
No full textAcute Delta(9)-tetrahydrocannabinol (THC) injection increased ERK pathway (ERK, pCREB, and c-fos) mostly in the caudate putamen and cerebellum. This effect underwent to homeostatic adaptation after chronic treatment. Moreover, chronic THC exposure induced increases in the ERK cascade (ERK, pCREB, and Fos B) in the prefrontal cortex and hippocampus, suggesting that different neuronal circuits seem to be involved in the early phase and late phase of exposure. The involvement of ERK pathway in cannabinoid chronic exposure was also confirmed in Ras-GRF1 knock out mice, a useful model where cannabinoid-induced ERK activation is lost. In fact, Ras-GRF1 ko mice did not develop tolerance to THC analgesic and hypolocomotor effect. Our data suggest that ERK cascade could play a pivotal role in the induction of synaptic plasticity due to cannabinoid chronic exposure
Chronic treatment with a synthetic cannabinoid CP-55,940 alters G-protein expression in the rat central nervous system
No full textProlonged exposure of rats to the synthetic cannabinoid receptor ligand, CP-55,940 (0.4 mg/kg, i.p. for 11 days), induced tolerance to analgesia, to the reduction in spontaneous locomotor activity and the incidence of splayed hind limbs. One hour after the last injection on day 11, the rats were killed and in situ hybridization was used to investigate the effect of treatment on G-protein α-subunit expression throughout the brain. Chronic cannabinoid exposure markedly reduced Gα(s), Gα1 and Gα0 mRNA levels. The message for the αs-subunit was decreased in all the brain areas containing the basal autoradiographic signal; the decrease ranging from 25% in the thalamus to 45% in the mesencephalon. Also the basal Gal expression was reduced in tolerant rats showing the greatest decrease in the forebrain (63%) in the cerebellum (58%) and in the mesencephalon (38%). The reduction in Gα0 expression (25%) was more localized, being present only in the rostral portion of the brain (cortex, striatum and olfactory area). The alterations in α-subunits gene expression were not followed by any change in the amount of proteins. Our results indicate that, besides the receptor modification, alteration to the G-protein expression could be a molecular event associated with the development of cannnabinoid tolerance
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