Failure to replicate an environmental effect of morphine hydrochloride consumption : a possible psychopharmacogenetic link (original) (raw)
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British Journal of Pharmacology, 1982
1 Rats are capable of consuming solutions of morphine sulphate in drinking water ad libitum in the absence of taste-masking chemicals and without the need for scheduled provision or prior parenteral administration of the drug. 2 The success of this method depends on the initial provision of a 0.1 mg/ml solution of morphine sulphate. 3 When the drug concentration is increased to 0.4 mg/ml, the rats achieve an average daily intake of 50 mg/kg body wt. each. 4 Daily intake of morphine may be increased by at least about three fold by increasing the drug concentration to 1.2 mg/ml. 5 Oral morphine administration causes only a moderate loss in body weight. 6 Rats whose daily intake of the drug is 50 mg/kg exhibit tolerance to the analgesic action of morphine and show a drastic loss in body weight at 24 h after withdrawal and most of the behavioural symptoms of the naloxone-precipitated withdrawal syndrome. 7 It is suggested that this simple method of morphine administration is suitable for further biochemical and behavioural studies of the actions of the drug.
A Novel Morphine Drinking Model of Opioid Dependence in Rats
International Journal of Molecular Sciences, 2022
An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants’ presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg/mL) solutions for two weeks. Then, quinine wa...
No psychological dependence after oral administration of morphine to rats
Neuroscience Letters, 1992
Rats subjected to forced oral self-administration of morphine solutions without or in combination with two daily i.p. injections of morphine preferred drinking water when this was offered in addition to morphine solutions. The daily intake of morphine during the terminal phase of self-administration of morphine was 50-80 mg/kg (oral application alone) or 270 mg/kg (oral and i.p. application). Morphine treated animals showed withdrawal symptoms on administration of naloxone 1 mg/kg i.p. during the period of self-administration, but not when they had started drinking exclusively water. The tail-flick test revealed no tolerance during prolonged treatment with morphine. The results indicate that no psychological dependence developed when morphine was applied orally and regularly.
Pharmacology, Biochemistry and Behavior, 1984
Brattleboro rats placed in metabolism cages were injected with morphine (Mor), naloxone (Nal), D-and L-aspartic acid (D-and L-Asp), D-phenylalanine (D-Phe), D-leucine (D-Leu) and prolyl-leucyl-glycinamide (PLG), alone and in suitable combinations. Food and fluid intake, urine outflow, faeces weight, rectal temperature and urinary osmolality were determined at the end of seven hours period of time. Mor, Nal, D-Asp and PLG alone caused a significant decrease in food and fluid intake, urine volume and faeces weight and a significant increase in urinary osmolality being the osmolality of the Mor, D-Asp and PLG injected groups higher than 300 mOsmol/kg. The combination of Nal with Mor, D-Asp and PLG appeared to intensify the changes induced by Mor, D-Asp and PLG whereas L-Asp antagonized the majority of changes caused by Mor or PLG. The results were discussed in the light of the previous experimental findings. DI Brattleboro rats Food intake Fluid intake Urine volume Faeces weight Rectal temperature Urine osmolality Morphine Naloxone D-and L-Aspartic acid D-Phenylalanine D-Leucine PLG
Small doses of morphine enhance voluntary intake of a solution of only ethanol and water
Bulletin of the Psychonomic Society, 1988
Rats, subsequent to havin g an extensive hi story of intake of alcoholic beverages, were placed on a schedul e of water depr ivation . Each day , the y were given a 2-h opportunity to tak e either a 6% solution of ethanol (6 g of ethanol and 94 g of tap water for each 100 g of fluid) or wat er . Across daily opportuniti es, intakes of th e ethanol solution and water stabilized, with rats taking about 1.0 g/kg of ethanol. Then , immediately prior to some sessions, rats were given injection s of either placebo, or 1.0 or 2.0 mg/kg morphine. On days of administration of morphine, rats took considerably more etha nol than on days of placebo administ ration, with a mean increment of about 0.9 g/kg. This findin g supports results of similar exper iments and lend s credence to the idea that differential functioning of endogenous opioid systems may be a salient feature of differenti al intake of alcoholic bever ages.
Genetic correlates of morphine withdrawal in 14 inbred mouse strains
Drug and Alcohol Dependence, 2009
Male mice from 14 standard inbred strains were exposed to morphine in a sustained released preparation injected subcutaneously. Five hours later withdrawal was precipitated by intraperitoneal injection of naloxone. Mice were tested from 0 to 15 min after naloxone for withdrawal jumping behavior, and then from minute 15-16 for other signs, including boli count, presence of soft stool, lacrimation, "wet dog" shakes, and air chewing. They were also assessed for change in body temperature 17 min after naloxone. Strains differed markedly in the severity of withdrawal for jumping, change in body temperature, and number of fecal boli. Strains also differed in percentage of animals displaying soft stool and air chewing behavior. The other two signs were seen at too low frequency for analysis. Correlations of strain mean withdrawal severity with other responses to morphine and other abused drugs showed that high morphine withdrawal jumping and low change in body temperature were both genetically related to high morphine consumption, but not generally to other measures of morphine withdrawal or morphine sensitivity. Published by Elsevier Ireland Ltd.
The concentration of morphine in serum of rats made dependent using a drug-admixed food method
Pharmacology, Biochemistry and Behavior, 1988
present study reports on the induction of physical dependence in rats using morphine-admixed food and addresses the question of the resulting concentration of morphine in serum. The stability of morphine in food is good, since no decrease in concentration could be observed. The concentration of morphine in serum during the experiment was measured using a radioimmunoassay technique. A correlation was found between the food intake during a 7-hour period and the concentration of morphine in the serum at the end of that period, both for a 1 g/kg and a 2 g/kg batch of morphine-admixed food. The concentration of morphine in serum was also found to be dose-related during a period of 6-23 days when the rats were fed for a prolonged period. ARer long-term administration of I g/kg morphine in food a steady-state level of about 0.5 mg/I serum was obtained. Similarly with 2 g/kg morphine in food a steady-state level of 0.8-1.1 mg/l serum was reached. After withdrawal of morphine the serum concentration of morphine dropped to 0. l mg/l within 24 hours and to below the detection limit within 48 hours. During the withdrawal period sharp drops were noted in body weight (20%) and food intake (50%) after one day.
A small dose of morphine increases intake of and preference for isotonic saline among rats
Pharmacology Biochemistry and Behavior, 1988
BERTINO, M, M L ABELSON, S H MARGLIN, R NEUMAN, C A BURKHARDT AND L D REID A small dose oJ morphuze m~ reases tntal, e of and preJeren¢ e Jor tsotomc sahne among rats PHARMACOL BIOCHEM BEHAV 29(3) 617-623, 1988 --Water-deprived rats were given hourly opportunities to ingest physiological sahne and water for a number of days until they were taking substantml amounts of both solutions Prior to some opportumtles to mgest, they were rejected with either morphine (2 0 mg/kg) or a placebo Across a variety of procedures, morphine increased retake of and. in 1-hr tests, increased preference for 0 ~/~ NaC1 Intake of 1 5% NaCI also increased after admlmstratlon of morphine These data suggest that endogenous oplolds are revolved in sodium retake These data also provide further support for the idea that one or more of the endogenous oplold systems are revolved In the regulation of ingestion