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At least 19 recordsLinked to original sources
PubMed1977

On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine.

The role of ascending noradrenergic (NA) and dopaminergic (DA) systems in intravenous self-administration of cocaine in rats was investigated by examining the effects of 6-hydroxydopamine-induced lesions of these systems on responding for the drug on a FR-1 schedule of reinforcement. Lesions of the dorsal and ventral NA bundles that reduced hippocampal-cortical NA by 96% and hypothalamic NA by 72% failed to have any effects on responding for cocaine. Lesions of the nucleus accumbens that reduced the DA content of this nucleus by 90% resulted in a significant and long-lasting (15 days) reduction in self-administration of cocaine. Apomorphine self-administration was not affected in the same animals. Identical lesions of the n accumbens had only transient (2-3 days) effects on food-reinforced operant responding, suggesting that the prolonged disruption of cocaine self-administration was not the result of motor deficits. The results are discussed with reference to the possibility that DA terminals in the n accumbens may mediate some of the positive reinforcing properties of cocaine.

Animals↗
PubMed2026

Refinement of Nucleus Accumbens Neuronal Dynamics during Cocaine Self-Administration Training.

Drug addiction is an acquired motivational-behavioral state that begins with drug taking, which is composed of a series of phases, including initial acquisition, stabilization, habituation, and maintenance. In rodent models of cocaine self-administration, the forebrain region nucleus accumbens (NAc) has been critically implicated in the acquisition-maintenance process of drug-taking and drug-seeking behaviors. However, it remains unknown how NAc neurons shift their activity patterns in response to these phasic transitions during cocaine taking. To examine this, we used GCaMP6m-based in vivo Ca2+ imaging in male mice to monitor activities of principal medium spiny neurons (MSNs) in the NAc across 11 d of cocaine self-administration. Behaviorally, mice exhibited progressive stabilization of operant responding and locomotion across 11 d of cocaine self-administration. During the early training days, we detected a portion of NAc neurons-a potential neuronal ensemble-that exhibited increased activities temporally contingent to the lever-press for cocaine. The number of NAc neurons exhibiting contingent activity increased progressively over the first three training days and then decreased gradually during the later training days, exhibiting expansion-refinement dynamics that may correspond to the acquisition and subsequent stabilization/maintenance of cocaine self-administration. Using a neuron-tracking technique, we found that the lever-press-contingent NAc ensemble exhibited substantial compositional dynamics, with neurons dropping into and out across training days. These activity features of lever-press-contingent neurons may represent key circuit dynamics of the NAc that transition the acquisition toward the maintenance of cocaine-taking behavior.

Animals↗
PubMed1979

Effects of the neuropeptide DG-AVP on morphine and food self-administration by dependent rhesus monkey.

Pretreatment with the neuropeptide DG-AVP (desglycrinamide9-arginine8-vasopressin) at two dose levels (25 and 125 mcg/kg) did not reduce intravenous morphine self-administration (0.25 mg/kg/inj) by morpine dependent monkeys, in comparison to pretreatment with saline or DG-AVP vehicle placebo. Food self-administration was also unaffected by DG-AVP pretreatment in comparison to control conditions. These data do not confirm previous reports of a dose-dependent suppression of heroin self-administration in rat following DG-AVP pretreatment [14].

Animals↗
PubMed1978

The effect of housing and gender on morphine self-administration in rats.

To determine the effect of housing conditions on morphine self-administration, rats isolated in standard laboratory cages and rats living socially in a large open box (8.8 m2) were given morphine in solution (0.5 mg/ml) as their only source of fluid for 57 days. They were then exposed to a series of 3-day cycles previously shown by Nichols et al. (1956) to increase self-administration of morphine in caged rats. On morphine/water choice days late in the period of forced consumption, between the Nichols cycles, and during a subsequent period of abstinence, the isolated rats drank significantly more morphine solution than the social rats, and the females drank significantly more morphine solution than the males. During the four choice days in the Nichols Cycle Period the isolated rats increased their consumption, but the socially housed animals decreased theirs.

Animals↗
PubMed1979

[A new method for enteral self administration of psychotropic drugs in the rhesus monkey (author's transl)].

This surgical method for the parenteral self administration of psychoactive substances in the Rhesus monkey is a modified gastrostomy. Success is warranted with a catheter-model which can be fixed at the inner wall of the abdomen. The catheter is placed subcutaneously until it leaves between the shoulders. Additionally all monkeys received leather corsets. This method has proved to be very safe in long-time self administration of drugs in the Rhesus monkey.

Animals↗
PubMed1978

Comparative effects of cocaine and pseudococaine on EEG activities, cardiorespiratory functions, and self-administration behavior in the rhesus monkey.

The effects of cocaine and pseudococaine on the EEGs, heart and respiratory rates, and self-administration behavior were studied in rhesus monkeys. An intravenous injection of cocaine (2.5 and 4.0 mg/kg) in the monkey produced low-voltage fast waves (LVFWs) in the EEGs and behavioral hyperexcitation accompanied by marked increases in the heart and respiratory rates with mydriasis and excessive salivation. In contrast, pseudococaine produced high-voltage slow waves (HVSWs) in the EEGs and behavioral depression accompanied by the same symptoms of the autonomic functions as those produced by cocaine. Both isomers were self-administered by the monkeys. During cocaine self-administration sessions, the animals showed hyperexcitation in their overall behavior, while with pseudococaine they showed almost normal behavioral responses. These results suggest that cocaine produced excitatory effects and pseudococaine inhibitory effects on the EEGs and behavior. Both isomers stimulate the heart and respiratory rates, and were self-administered by the monkeys.

Animals↗
PubMed1978

Changes in morphine self-administration after tel-diencephalic lesions in rats.

Rats were trained to bar-press for intravenous infusions of morphine sulfate during 1-h daily test sessions. Rates of morphine self-administration were enhanced by lesions of the frontal cortex and hippocampus and transiently reduced by lesions of the medial forebrain bundle and medial thalamus. Dose-response studies indicated that sensitivity to morphine's rewarding property was decreased by frontal cortical and hippocampal lesions. Lesions of the posterior cortex, the tuberculum olfactorium, and the nucleus accumbens had no effect on self-administration behavior. The results are discussed in relation to previous findings with caudate and brainstem lesions. A neuroanatomical substrate for morphine reinforcement is suggested.

Animals↗
PubMed1977

[Morphine self-administration added to food conditioning: methodological variant in rats].

Rats with permanent intra-jugular cannula are submitted to an alimentary operant reinforcement schedule with fixed ratio type FR 1, FR5, then FR 20. As a result, the animals are self administering (together with the alimentary inducer) a slow (about 5 sec) intravenous infusion of morphine (0.05 mg/kg). 20 per cent only of the experimental population exhibit a psychogenic dependance afterward. On the other hand, the animals for which morphine self-administration has been substituted to the alimentary reinforcement without respecting a transitory period combining both types of reinforcement have never shown any tendancy toward morphine self-administration. The lack of positive results could be related to the marked duration of the self-injection.

Animals↗
PubMed1975

REM sleep distributions in post-addict rats relapsing to morphine self-administration: effects of naloxone subcutaneous pellets.

Female Sprague-Dawley rats were prepared with chronic cortical and temporalis muscle electrodes and i.v. cannulas. They were administered i.v. injections of morphine to produce tolerance and physical dependence, then trained to lever press for i.v. self-injections of morphine (10 mg/kg) to maintain dependence. They were subsequently withdrawn for two weeks, implanted subcutaneously with one or two pellets of naloxone base, 100 mg each, or placebo pellets, returned to the experimental cages and allowed to relapse to self-administration of either saline or morphine. Rats with placebo pellets relapsed to morphine self-administration and reestablished the dependence state. However, rats implanted with naloxone and then permitted to self-administer morphine extinguished their lever pressing ("drug-seeking behavior"). Similar results were obtained with rats implanted with placebo pellets and self-administering saline. The self-injections of morphine by rats implanted with placebo pellets severely suppressed REM sleep and altered its normal distribution. Rats implanted with naloxone pellets and that subsequently extinguished their lever pressing, however, did not exhibit a change in REM sleep distributions. Similarly, self-injections of isotonic saline did not exert an effect on REM sleep distributions. These findings suggest that a correlation between REM sleep distributions, drug-seeking behavior, and morphine-naloxone interaction prevailed.

Animals↗
PubMed1976

Opiate antagonists and the modification of heroin self-administration behavior in man: an experimental study.

The heroin self-administration behavior of 8 inpatient heroin addicts was examined for 10 days under blocked (i.e., following ingestion of narcotic antagonists--naloxone or naltrexone) and unblocked (no antagonist) conditions. In the unblocked state, subjects injected all the available heroin, but they ceased heroin use almost completely following antagonist administration. Possible explanations for these results are discussed along with their implications for treatment.

Adult↗
PubMed1979

Opioids: similarity between evaluations of subjective effects and animal self-administration results.

Abuse potential studies of 33 morphine-like analgesics were compared in humans and monkeys. The results of intravenous self-administration studies in rhesus monkeys were correlated with measures of morphine-like signs, symptoms, and subjective effects in ex-addicts. Each set of data was assigned to a position in a 3 x 3 contingency table dependent upon whether the results were yes, no, or equivocal. Of the 33 drugs, 29 were given identical classifications in both the human and animal test procedures. This good concordance between the human and animal results further validates each procedure and suggests the possibility that both the human and animal procedures are measuring a common underlying pharmacological property which relates to abuse potential of drugs.

Animals↗
PubMed1978

Effects of passive immunization against morphine on heroin self-administration.

Antimorphine antibodies produced in Rhesus monkeys immunized with morphine-6-hemisuccinate-BSA were passively administered to recipient monkeys trained to self-administer heroin and cocaine. Following antibody administration, changes in heroin self-administration behavior were observed which were similar to those achieved with low doses of naloxone. Both manipulations increased heroin self-administration without affecting cocaine responding.

Animals↗
PubMedDate not supplied

Noradrenergic role in the self-administration of morphine or amphetamine.

The role of brain noradrenergic neurons in mediating the reinforcing properties of small intravenous doses of morphine and d-amphetamine was investigated by pretreatment of rats with the norepinephrine-depleting agents diethyldithiocarbamate and U-14,624, inhibitors of dopamine-beta-hydroxylase (DBH). Such treatment prevented the reacquisition of a self-administration response (bar-press) for morphine (32 mug/kg/injection) or d-amphetamine (15 mug/kg/injection) made available on a CRF schedule. Pretreatment with a DBH inhibitor also prevented the development of a secondary (conditioned) reinforcer based on primary reinforcement assosiated with either drug. Observations indicating that the orienting reflex was intact are taken as evidence that depressant effects of the DBH inhibitors were not severe enough to disrupt the associative process. Therefore, any effect on learning does not seem sufficient to explain the present results. Thus, it is inferred that the mechanisms mediating reinforcement for both morphine and amphetamine were disrupted by the inhibition of central noradrenergic functions.

Animals↗
PubMed1979

Dose and physical dependence as factors in the self-administration of morphine by rats.

Groups of naive rats were offered morphine sulfate for self-admininstration in doses of 0.0032-10 mg/kg for 6 days. On day 7 saline was substituted for morphine. Loss of weight was taken as physiological evidence of dependence. Rats that did not lose weight formed a single population whose mean injection rate did not differ from control rats receiving only saline injections. Injection rates for rats losing weight were log-normally distributed, and the mean of the logarithms of the injection rates was linearly related to the logarithm of the dose. Mean daily injection rates averaged 12 for controls, 23 at 10 mg/kg, and 411 at 0.01 mg/kg. A transient increase in morphine intake after an injection of nalorphine was taken as behavioral evidence of dependence. Nalorphine increased morphine intake when rats were self-injecting 0.32 and 1.0 mg/kg of morphine, but not 0.032 or 0.1 mg/kg. The reinforcing property of morphine may occur without behavioral evidence of dependence.

Animals↗
PubMed1979

Intraventricular self-administration of acetaldehyde, but not ethanol, in naive laboratory rats.

For 11 consecutive days, naive rats were maintained in operant chambers where they were given the opportunity to self-administer acetaldehyde (1,2, or 5% v/v), ethanol (2 or 10% v/v), or pH control solutions directly into the cerebral ventricles. Only the animals that had access to the 2 and 5% acetaldehyde solutions showed rates of lever pressing significantly higher than controls. It is suggested that acetaldehyde rather than ethanol itself may mediate the positive reinforcing effects of ethanol in the brain.

Acetaldehyde↗