Biomedical subjects

L D Reid

Publications and source records attributed to L D Reid.

At least 37 records · Page 2Linked to original sources

PubMed1992

Cocaine place preference is blocked by the delta-opioid receptor antagonist, naltrindole.

Naltrindole, a selective delta-opioid receptor antagonist, was evaluated for its potential to block the reinforcing properties of cocaine using a conditioned place pairing paradigm in Lewis rats. Cocaine HCl (15 mg/kg s.c.) produced a strong place preference which was significantly blocked in animals pretreated with naltrindole (3 mg/kg i.p.); naltrindole alone showed no reinforcing or aversive effects. The results suggest a novel approach for the treatment of cocaine abuse in man.

Animals↗

PubMed1992

Opioidergic modulation of cocaine conditioned place preferences.

Recent studies have begun to assess the utility of opioid agonists and antagonists for the treatment of cocaine addiction. The present studies assess the effects of naltrexone or methadone on cocaine's reinforcing properties using the conditioned place preference (CPP) test. The results indicate that a 56 mg/kg dose of naltrexone, given 4 hr prior to conditioning, attenuates cocaine's CPP. In contrast, methadone (8 mg/kg), given 1 hr prior to conditioning, enhanced cocaine's reinforcing properties. These results support the suggestion that opioid antagonists may have clinical utility in treating cocaine addiction. The results with methadone lead to a possible explanation for the higher rates of cocaine use in methadone-treated heroin addicts.

Analysis of Variance↗

PubMed1991

MDL72222, a serotonin 5-HT3 receptor antagonist, blocks MDMA's ability to establish a conditioned place preference.

Methylenedioxymethamphetamine (MDMA) has previously been shown to produce a positive conditioned place preference (CPP) among rats. Here the effects of doses of a specific 5-HT3 antagonist, MDL72222, on MDMA's ability to produce a CPP were assessed. A dose of MDL72222 (0.03 mg/kg) blocked the establishment of a MDMA CPP. These results support the suggestions that compounds affecting the 5-HT3 receptor may be of particular interest in studying the pharmacology of self-administered drugs.

3,4-Methylenedioxyamphetamine↗

PubMed1991

MDMA produces a conditioned place preference and elicits ejaculation in male rats: a modulatory role for the endogenous opioids.

Methylenedioxymethamphetamine (MDMA) can produce a conditioned place preference (CPP) among rats. The ability of MDMA to produce a CPP was assessed while some rats were under the influence of naltrexone, 56 mg/kg, given 4 h before conditioning. Naltrexone attenuated MDMA's ability to produce a CPP without completely blocking MDMA's effects. Having noticed previously the production of seminal plugs by rats receiving MDMA, the presence of seminal plugs was recorded across the 8 days of conditioning. Roughly half of the rats receiving 6.3 mg/kg of MDMA left plugs during the conditioning period, while over two-thirds of those receiving a combination of MDMA and naltrexone left plugs. A second study, assessing further doses of MDMA, tabulated the drug's effects on the production of seminal plugs across 3 h. Besides eliciting ejaculation, MDMA also led to increased urination and defecation and a loss of body weight. These results support suggestions that the endogenous opioids modulate the reinforcing properties of stimulant drugs and affect male sexuality.

3,4-Methylenedioxyamphetamine↗

PubMed1990

Modulation of ethanol-intake by morphine: evidence for a central site of action.

Previous studies have shown that subcutaneous administration of low doses of morphine increase, while subcutaneous naloxone decreases, ethanol-intake in rats. However, the site of action of morphine modulation of ethanol-intake remains unclear. In an attempt to elucidate this issue, seven graded doses of morphine were given intracerebroventricularly to rats 15 min prior to an opportunity to consume water and sweetened alcoholic beverage for 2 hr. Two lower doses of intracerebroventricular morphine (1, 3 micrograms) reliably increased ethanol-intake, while higher doses (3-30 micrograms) decreased intake of water. Preference ratios (ethanol-intake divided by total fluid-intake) were reliably increased by morphine doses of 1 microgram and higher. The present data provide support for a central site of morphine modulation of ethanol-intake.

Alcohol Drinking↗

PubMed1990

Using antagonists to assess neurochemical coding of a drug's ability to establish a conditioned place preference.

Rats were given morphine as an agent of putative conditioning to establish a place preference. Doses of 4 and 8 mg/kg of morphine did establish reliable conditioned place preferences (CPP's). Other rats were given one of the doses of morphine and one of a number of antagonists in procedures designed to assess which antagonists would specifically block morphine's ability to establish a CPP indicative of positivity. Doses of naloxone and larger doses of naltrexone but not smaller ones did antagonize morphine's effects. A dose of the benzodiazepine antagonist Ro 15-1788 did not attenuate morphine's effects. It was concluded that morphine's positivity is dependent upon actions by way of receptors sensitive to naloxone and naltrexone, but that morphine's positivity is less sensitive to naltrexone's effects than morphine's analgesia.

Analgesics↗

PubMed1990

Methylenedioxymethamphetamine's capacity to establish place preferences and modify intake of an alcoholic beverage.

Doses of 0.2, 2.0, 6.3 and 20.0 mg/kg 3,4-methylenedioxymethamphetamine (MDMA), a putative neurotoxin at serotonergic neurons and a recreational drug, were assessed using Sprague-Dawley rats in the conditioned place preference (CPP) test. Also, the drug's effects on intake of a sweetened ethanol solution (ES) was assessed. The CP testing involved multiple administrations of MDMA with frequent periodic testing (weekly for 4 weeks) of MDMA's effects. Doses of 2.0 and 6.3 mg/kg produced positive CPPs with every test. MDMA also affected rats' gain in body weight across the 4 weeks of dosing. The 2.0 mg/kg reliably incremented gain in body weight, while the 20.0 mg/kg dose reliably attenuated it. In the drinking experiment, water-deprived rats (22 h/day) were given daily opportunities to drink either tap water or a sweetened ES. When stable intakes were achieved, MDMA's effects were assessed across repeated daily administrations (12 days) and subsequently (16 days). MDMA, dose-relatedly, decreased intake of both ES and water with the highest dose leading to marked loss in body weight. Intakes of fluids were not modified markedly subsequent to dosing. In summary, MDMA is an agent that produces a positive CPP (providing further evidence for MDMA's abuse liability), produces changes in weight gain and nonselectively reduces fluid intake among fluid-deprived rats.

3,4-Methylenedioxyamphetamine↗

PubMed1989

Measuring morphine's capacity to establish a place preference.

A series of experiments are described providing an assessment of the procedures of conditioned place preference (CPP) testing involving an automated system having 12 separate chambers. Experiment 1 provides data to demonstrate (a) that in these chambers no initial preferences for one side over the other exists among rats, (b) that this neutrality of sides is not affected by session lengths between 15 and 60 min, and (c) that the optimal session length for tests in these chambers is on the order of 30 min. Experiment 2 demonstrates the stability of control groups' scores across a number of conditioning and testing sessions. Experiments 3 and 4 provide data to demonstrate (a) that a positive CPP can be established in our chambers using injections of morphine, (b) that a regimen of dosing with unequal numbers of days of putative and alternate conditioning is a reliable and conservative test of the opioid's ability to establish a CPP, and (c) that although the activity of rats decreases across a session, the general activity of rats before and after conditioning procedures is the same. Experiment 5 replicates the procedures employed by Scoles and Siegel (25) and demonstrates that the tendency for rats to explore novel environments is strong, and care must be taken to provide an opportunity for rats to pair different experiences with each side of the chamber in order for a CPP to emerge.

Animals↗

PubMed1989

PCP and conditioned place preferences.

Phencyclidine (PCP), in doses of 0.25, 0.35, and 0.45 mg/kg, was administered systemically to male Sprague-Dawley rats in order to determine if a positive conditioned place preference (CPP) could be achieved. Other subjects received systemic injections of morphine, 4.0 mg/kg, as a standard for comparison. At testing, rats receiving 0.45 mg/kg PCP showed a positive CPP compared to controls, as did rats receiving morphine. Previous research had shown that larger doses of PCP and prolonged times after PCP administration produced aversion as indexed by CPP testing. The narrow dose range and short time span in which PCP's positively reinforcing properties are apt to emerge may be related to PCP's psychotomimetic potential and to its ability to sustain its own intake even though aversive effects are often manifest.

Animals↗

PubMed1988

A small dose of morphine increases intake of and preference for isotonic saline among rats.

Water-deprived rats were given hourly opportunities to ingest physiological saline and water for a number of days until they were taking substantial amounts of both solutions. Prior to some opportunities to ingest, they were injected with either morphine (2.0 mg/kg) or a placebo. Across a variety of procedures, morphine increased intake of and, in 1-hr tests, increased preference for 0.9% NaCl. Intake of 1.5% NaCl also increased after administration of morphine. These data suggest that endogenous opioids are involved in sodium intake. These data also provide further support for the idea that one or more of the endogenous opioid systems are involved in the regulation of ingestion.

Animals↗

PubMed1988

Naloxone persistently modifies water-intake.

Rats, deprived of water for 19 hr, were given an opportunity to drink water for 30 min and for another 4.5 hr. Prior to drinking, rats were injected with saline or NX (2.5 mg/kg) to see if NX's effects persisted when given day after day. The findings confirmed that NX not only reduced intake but its effects showed no tolerance across consecutive administrations. Subsequently, when rats were deprived of water for 23.5 hr, NX produced a reliable decrease in intake. Intakes, however, were considerably greater than when subjects had an additional opportunity to drink.

Animals↗

PubMed1988

PCP, THC, ethanol, and morphine and consumption of palatable solutions.

Water-deprived rats were given daily opportunities (2.0-hr sessions) to take water or a sweet solution (20% or 24% sugar-water). After stable intakes of each fluid were achieved, the effects of phencyclidine hydrochloride (PCP), delta-9-tetrahydrocannabinol (THC), ethanol (E), and morphine (M) on intakes were tested. PCP, THC, and M all enhanced intake of the sweet solution, while E produced varying effects across doses tested. With other rats, nearly the same procedure was used except that the test solution presented with water was 0.9% sodium chloride. Doses of PCP enhanced intake of the salty solution. These data, combined with the data from similar studies of the effects of opioids and benzodiazepines, indicate that a wide variety of agents that are self-administered also modify intake of ingesta.

Animals↗

PubMed1986

The role of the mediobasal arcuate hypothalamus in relation to opioid systems in the control of ingestive behaviour in the rat.

Bilateral, radiofrequency lesions of the mediobasal arcuate hypothalamus (MBH) strongly depleted levels of immunoreactive (ir)-beta-endorphin (beta-EP) in the hypothalamus and other brain tissues: these changes reflect destruction of those beta-EP-containing perikarya which are located in the MBH. No change in plasma ir-beta-EP was seen. The ir-dynorphin (DYN) content of the hypothalamus was also depressed while that of ir-Met-enkephalin was unaffected. The fall in hypothalamic ir-beta-EP was correlated with the fall in that of ir-DYN. Lesioned rats displayed only a minor, transient reduction in rate of weight gain between days 3 and 9 postsurgery: this disappeared thereafter. Further, the lesion did not affect the pattern of weight loss and regain associated with 24 h food and water deprivation. Indeed, the total 24 h (daily) food intake (FI) and water intake (WI) of lesioned rats did not differ from that of sham animals while deprivation-induced hyperphagia and hyperdipsia was not attenuated by the lesions. Moreover, the ability of naltrexone to decrease FI and WI (during both dark and light phases of the daily cycle) was not altered by the lesions. These observations indicate that central beta-EP may not be essential for the maintenance of a normal 24 h FI and WI and that opioid antagonists do not act upon the MBH or upon central beta-EP neurones in their suppression of FI and WI. Further, they suggest that central beta-EP may not fulfil an essential role in the control of body weight in the rat. Lesioned rats did, however, reveal a shift in the diurnal rhythmicity of FI and WI reflected in a reduction in the dark:light ratios of these. An alteration in the diurnal rhythmicity of sleeping and core temperature, but not locomotor activity, was also seen. The shifts in hypothalamic ir-beta-EP and ir-DYN (but no other tissue levels of any peptide) were correlated with the magnitude of the shifts in diurnal rhythmicity of ingestive behaviour. Moreover, lesions caudal to the MBH (not affecting hypothalamic ir-beta-EP or ir-DYN) or dexamethasone treatment (which affects pituitary pools of ir-beta-EP and ir-DYN) did not modify these rhythms. Thus, in these respects, the effects are 'particular' to MBH lesions modifying hypothalamic ir-beta-EP and ir-DYN. The data suggest that the MBH may play a role in the modulation of the diurnal scheduling of ingestive behaviour in the rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Naloxone's effects on intake of sequentially presented fluids.

Fluid-deprived rats were presented with one of three types of palatable solutions for 15 min, followed by access to either the same solution or one of the other types for 15 min. The solutions were 5.3% sucrose, 0.9% salt solution, and tap water. Naloxone reduced intake of all solutions, as compared to placebo, regardless of type of fluid or order of presentation. Rats receiving water followed by sucrose solution reduced their intake of water under naloxone, but did subsequently take a considerable amount of sucrose solution showing that they were capable of drinking more. These findings indicate that naloxone's effects closely track ordinary satiation-effects, merely enhancing satiation-like functions at each instance of opportunity to take fluids.

Animals↗

PubMed1986

Demonstrating morphine's potentiating effects on sucrose-intake.

Mildly deprived rats (18-hr of deprivation of water) were given the opportunity to take a solution of sucrose daily for periods of either 10, 18, 31, 56, or 100 min. After daily intakes stabilized and prior to a session, rats were given an injection of either morphine sulfate, 1.0 mg/kg, or naloxone hydrochloride, 2.5 mg/kg, an agonist and an antagonist, respectively, at the opioid receptors. Naloxone, as expected, decreased intakes regardless of the test-session's length. Morphine decreased intakes of the shorter sessions, but increased intake of the longest session. Subsequently, injections of morphine were given 56 min into a 100-min session. These injections also increased intake. Morphine's effects in potentiating intake seem to have special relevance with respect to the continuance of ingestion. Variations across experiments, in duration of test-sessions, could account for the variations in conclusions drawn about whether or not morphine and other agonists potentiate intake of ingesta.

Animals↗

PubMed1986

Opioids and intake of alcoholic beverages.

Rats were given a daily opportunity to consume a sweetened ethanol solution (ES) or water until they took about 2.0 g/kg of pure ethanol (E) during 1.5 hr/day. Then, rats were given one of a number of opioids before an opportunity to drink. Some opioids, e.g., morphine (MOR), methadone, and fentanyl, at small doses, increase ES-intake; some decrease intakes, e.g., naloxone (NX) and MR 2266. Diprenorphine, a mixed agonist-antagonist having no analgesic potential and blocking other opioids' analgesia, increases ES-intake across a wide range of doses beginning with 0.003 mg/kg.

Alcohol Drinking↗

PubMed1985

Toward understanding ethanol's capacity to be reinforcing: a conditioned place preference following injections of ethanol.

Rats that had previously consumed a 6% ethanol (ETOH) solution daily for 26 days and rats without such a history served as subjects in a test for the ability of ETOH to establish a conditioned place preference. The time of putative conditioning was from 4 to 8 min after injections of ETOH, 1 g/kg. The combination of programming the period of putative conditioning to be shortly after injections and using rats habituated to drinking ETOH allowed a conditioned place preference to emerge after only a few conditioning trials. Such a result potentially reveals features of the way ETOH achieves its reinforcing capability and sets the stage for understanding the mechanism of that reinforcement.

Animals↗

PubMed1985

Selected opioids and responding for intracranial reinforcement.

Rats fixed with chronically indwelling electrodes for intracranial stimulation (ICS) of the lateral hypothalamus pressed a lever during daily sessions for a fixed intensity of ICS. Before some sessions, they were given placebo, or ethylketocyclazocine (EKC) in racemic or isomeric forms [either (+)EKC or (-)EKC]. Naloxone (NX) was also given with the agents. The racemate facilitated pressing across a narrow range of small doses (centered about 0.02 mg/kg). At no dose did (-)EKC, a potent analgesic, facilitate pressing and typically depressed it. (+)EKC, at doses of 0.04 and 0.08 mg/kg, facilited pressing. These data provide further confirmation that opioid analgesia and ability to enhance pressing are separable. When NX was given with a large dose of the racemate, paradoxically pressing for ICS was facilitated. Apparently, NX selectively blocked the effects of (-)EKC. SKF 10047 was also administered in racemic and isomeric forms. All three forms produced some facilitation of pressing at small doses (e.g., 0.75 mg/kg) and depressed pressing at large doses (e.g., 5.0 mg/kg).

Animals↗