SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Contralateral lesions of ventromedial and lateral hypothalamic nuclei inhibited hypothalamic self-stimulation in rabbits. Intracerebroventricular injection of metenkephalin evoked the restoration of self-stimulation behavior.
The stimulation of the brain in self-stimulation situation activated the motor behaviour. The activity of the motor behaviour versus duration of the movements which define the motor activity is a decreasing function. The effect of stimulation versus duration or the strength of stimulation is an increasing function. The solutions of equation having made after comparing these two functions demonstrate the relations between the motor behaviour and stimulation parameters.
An extensive mapping of the caudate-putamen in rat for intracranial self-stimulation (ICS) site was undertaken to provide addtional support for the role of dopamine in brain-stimulation reward. Eight-seven per cent of the placements in the neostriatum supported ICS, with self-stimulation rates greater than 250/15 min at 56% of these sites. Electrical stimulation also elicited rearing and clonus, and contralateral body turn, both of which varied in magnitude between animals. In a second experiment, animals were prepared with electrodes aimed at the lateral caudateputamen. Those subjects displaying ICS subsequently received 6-hydroxydopamine lesions to the dopamine cell bodies in the substantia nigra pars compacta, either ipsilateral or contralateral to the electrode. The destruction of the dopamine cell bodies attenuated ICS in both groups during the first post-lesion test sessions. However, the rates in the ipsilateral group declined to between 2 and 9% of control scores, whereas the rate in the contralateral group improved over testing to 72% of control values, 28 days after the lesion. On the basis of these data, it was concluded that unilateral destruction of the dopaminergic nigro-neostriatal bundle (NSB) has two effects on ICS behavior. First, unilateral reduction of neostriatal dopamine is accompanied by a loss of brain-stimulation reward at sites normally innervated by the NSB, specifically the caudate-putamen. Secondly, lesions of the NSB produce a general disruption in bar-pressing behavior, as evidenced by the attenuation of ICS following contralateral lesions.
Despite numerous pharmacological investigations of intracranial self-stimulation (ICSS), the substrates of this behavior have yet to be completely understood. In view of the likelihood that inadequate methodology has hindered the quest for these substrates, the present review was undertaken. Criteria for ICSS methodology should include not only the ability to discriminate reward from gross performance deficit, but also adequate capacity (ability to generate experimental data at a reasonable rate). For numerous reasons, bar-pressing on a continuous reinforcement schedule fails the first criterion despite its ease and rapidity. The use of partial reinforcement schedules may alleviate some of these shortcomings. Analysis of drug-induced response decrement patterns can discriminate gross motoric incapacity from other variables, although the question of subtle response maintenance deficits remains to be answered. Measurements of response rates using alternative operants do not differentiate reward and performance adequately. More promising, "rate-free" measures using locomotion as an operant include the two-platform method of Valenstein and the "locus of rise" method. Comparison of drug effects on ICSS with those on alternate tasks are fraught with pitfalls including the problems of assuring equivalent rates and patterns of responding. The use of differential electrode placements is ideally suited for neurochemically well-characterized drugs, particularly if "double dissociations" can be established during studies of multiple placements. Presentation of different current intensities or frequencies permits the compilation of rate-intensity functions, and drug-induced shifts in these functions have considerable analytical power. Self-regulation of current intensity constitutes a powerful tool that has yet to realize its full potential in the pharmacological study of ICSS. Extensive studies involving self-regulation of stimulation duration ("shuttlebox" studies) suggest that this method may be highly versatile despite several practical difficulties. It is concluded that at least six of these methods appear to do a reasonable job of excluding gross performance deficit. However, the possible influences of other factors, such as subtle response maintenance deficit, incentive or arousal, remain to be resolved in view of the multifactorial nature of ICSS. Multiple tests for ICSS drug or lesion studies are advocated whenever feasible, as no single test appears capable of resolving all theoretical complexities.
Multiple operants have been used to assess the effects of drugs on self-stimulation. It has typically been assumed that changing the operant used to obtain brain stimulation represents a simple performance manipulation. However, the validity of this assumption has been challenged by several research findings. The present study sought to clarify the role of response topography and slight differences in electrode placement on operant-induced shifts in self-stimulation thresholds and response rates. Thresholds and rates were determined for three operants (leverpressing, nosepoking and omnidirectional leverpressing) using two bilaterally placed electrodes. In addition, the response topographies used to perform each operant were evaluated. It was found that the relationship between the thresholds and rates produced by the operants was more dependent on the electrode placement than operant or subject-specific factors. The results of this experiment suggest that the characteristics of the stimulation site determine the relationship among different operants. This finding may be due to differences in the reward substrate or stimulation-induced behaviors activated at various brain loci.
It is unclear whether behavioral depression and suppression of food intake by cholecystokinin (CCK) is contributed to by aversive gastrointestinal effects such as nausea. In the present study we examined the effect of a new antiemetic agent, ondansetron, a specific antagonist of 5-HT3 receptors, on suppression of variable-interval self-stimulation by the CCK analogue caerulein. Responding by rats for brain-stimulation reward is especially sensitive to CCK, and provides a convenient means of investigating this question. Caerulein (30 micrograms/kg, s.c.), injected alone, was followed by a profound (ca. 80%) reduction in the rate of self-stimulation, lasting about 30 min. Ondansetron (1.0-1000 micrograms/kg, s.c.) injected on its own had no effect on self-stimulation rate, and a 100-micrograms/kg dose did not lessen the depressant action of caerulein. The behavioural depressant effects of CCK are thus unlikely to depend on brain mechanisms for nausea and vomiting involving 5-HT3 receptors.
In a series of experiments in animals and in man several authors have shown that sensory stimulation induces low voltage fast activity in the EEG. The problem to be studied in this work is related to the EEG changes produced by self-stimulation. A group of human subjects were instructed to be self-stimulated with clicks and flashes of light randomly applied by themselves. When the subjects were with the eyes closed and in resting state, alpha rhythm was predominantly recorded in the EEG. However, during acoustic or visual stimulation a low voltage fast activity was predominantly observed in the EEG. In self-administration of the stimulus a low voltage fast activity was recorded in the EEG several seconds before the stimulus application. These results suggest that the activation of a complex neuronal mechanism involved in the volitive response, as well as anxiety and attentive states of the subject occurring before the actual stimulation to select the moment at which the stimulus has to be applied, can be responsible for the blocking of the alpha rhythm previously to the flashes of light and clicks presentation.
Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.
Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.
Changes in the activity of dopaminergic neurons associated with intracranial self-stimulation of the ventral tegmentum were assessed by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of aromatic amino acid decarboxylase by NSD-1015. When compared to implanted unstimulated controls, DOPA concentrations were elevated significantly in the nucleus accumbens, striatum and olfactory tubercle in the hemisphere ipsilateral to the electrode, after a 30 min session of self-stimulation. The concentration of DOPA in the contralateral nucleus accumbens and striatum did not differ from control levels, although relative to control values it was significantly increased in the contralateral olfactory tubercle. A similar analysis of in vivo tyrosine hydroxylase activity in these brain regions following a 30 min session of lever pressing for food reward on a fixed-ratio (FR-8) schedule failed to reveal any significant changes relative to control subjects. These results are consistent with a role for dopamine in brain-stimulation reward obtained from electrical stimulation of the ventral tegmental area but do not provide evidence for dopaminergic mediation of the rewarding properties of food.
Explore the source record for details and available documents.
Depriving rats of rapid eye movement (REM) sleep was shown to lower their thresholds and raise their response rates for rewarding brain stimulation. Conversely, allowing rats to self-stimulate while they were being deprived of this sleep form reduced the amount of REM rebound during recovery from deprivation. These results demonstrate a reciprocal relation between rewarding brain stimulation and REM sleep.
The acquisition of discriminative behavior was studied in three autistic children with high-frequency self-stimulatory behavior. It was found that: (a) the children did not acquire the discrimination while engaged in self-stimulation; (b) suppression of self-stimulation produced an increase in correct responding, with eventual acquisition of the discrimination; (c) successful discrimination learning was always associated with a reduction in self-stimulatory behavior, even when aversive stimuli were not used for suppression.
Low doses (300 micrograms/kg-1.0 mg/kg) of the novel beta-carboline, ZK 91 296, a putative agonist at the benzodiazepine receptor, produced a significant increase in the rate of variable-interval self-stimulation responding, similar to that found with typical benzodiazepines. This effect was blocked by simultaneous administration of the specific benzodiazepine-receptor antagonists Ro 15-1788 (2.0 mg/kg), and ZK 93 426 (10 mg/kg). Neither antagonist, ZK 93 426 (100 micrograms/kg-10 mg/kg) or Ro 15-1788 (2.0 mg/kg), had any effect on self-stimulation when given alone. Unlike all benzodiazepine-receptor agonists previously tested, higher doses of ZK 91 296 did not depress self-stimulation response rates, even at a dose-level 100 times greater than the maximally stimulant dose. It is uncertain why ZK 91 296 lacks depressant effects: available evidence does not conclusively favour any single current explanation, but is consistent with it acting as a "partial" agonist.
Male Wistar rats were socially isolated from the 17th day of birth. Ventral tegmental area (VTA) of a half of the 17th-day rats was unilaterally damaged with intrastructural administration of kainic acid. In adult rats (both raised in groups and in isolation) amphetamine (1 mg/kg) facilitated self-stimulation of the lateral hypothalamus (by 37%). Social isolation increased the sensitivity of dopaminergic system only in rats with VTA lesions which was manifested in promoting self-stimulation after administration of amphetamine, though the level and turnover of tegmental dopamine was decreased. 6-Hydroxydopamine (75 mcg intracisternally), a catecholaminergic neurotoxin, significantly inhibited self-stimulation in isolated rats and decreased catecholamine levels in the lateral hypothalamus. The neurotoxic effect of 6-hydroxydopamine was abolished by amphetamine, probably, owing to enhancement of the functional activity of parabiotically living neuronal structures of the mesocorticolimbic dopaminergic system of the brain.
Rats were implanted with stimulating electrodes aimed either at the medial forebrain bundle-lateral hypothalamus (MFB-LH) or the midbrain-central gray (MID-GG), and were trained to lever-press for brain self-stimulation on a fixed ratio: 15 schedule of reinforcement. The dose-dependent effects of morphine (0.1-3.0 mg/kg), naloxone (0.1-30 mg/kg), and naltrexone (0.1-30 mg/kg) were then determined during 1 h test sessions. Both naloxone and naltrexone decreased the rate of responding in the MFB-LH as well as in the MID-CG. However, decrements in response rates were produced in the MID-CG by both naloxone and naltrexone at one tenth the doses required to produce similar decrements with electrodes in the MFB-LH. Dose-dependent decreases in response rates produced morphine occurred at the same doses in the two electrode sites. At both sites, the decreases in response rates produced by the highest dose of morphine were antagonized completely by a low dose of naloxone (0.1 mg/kg). At an intermediate dose of naloxone (1.0 mg/kg), antagonism occurred in the MFB-LH but not in the MID-CG. At a high dose of naloxone (10 mg/kg), a depression in lever-pressing occurred at both sites in the morphine-treated animal indicating that the depressive action predominated over antagonism. These data explain the lack of consistency of the effects of naloxone on brain self-stimulation previously reported by different laboratories, and demonstrate that the use of partial reinforcement schedules in a rational approach to the evaluation of opioid effects on brain self-stimulation behavior.
The purpose of this research was to determine whether brain stimulation reward and exploration are induced by activation of the same set of neurons along the medial forebrain bundle. The behavioral version of the collision test was utilized with electrodes in the lateral hypothalamus (LH) and the ventral tegmental area (VTA). A collision effect obtained between LH and VTA in one behavior at the exclusion of the other was treated as evidence of the involvement of two different sets of fibers. In 4 rats, a collision effect was observed only in self-stimulation, whereas in 1 rat, a collision was obtained in exploration at the exclusion of self-stimulation. Three animals showed no collision in either behavior. These data suggest that coexistence of self-stimulation and exploration following medial forebrain bundle stimulation can be explained by current spread on two different sets of fibers.
These experiments tested the hypothesis that the suppressing and facilitating effects of morphine on intracranial self-stimulation (ICS) (measured 1 h and 3 h post-injection, respectively) are influenced by associative, non-pharmacological factors. Experiment 1 confirmed previous demonstrations that the facilitation of ICS by morphine (10 mg/kg) develops with repeated drug exposures. Once ICS facilitation had developed, the effect was mimicked by saline injection in most subjects. In a separate group of animals, previous exposure to morphine in the home cage prevented drug-induced facilitation of ICS. Tolerance to ICS suppression developed after repeated pairings of the drug and the ICS chambers, but not when the drug had previously been received in the home cage. Experiment 2 examined the effect of low (0.3, 1, 3 mg/kg) doses of chronic morphine on ICS. Facilitation was observed with 1 and 3 mg/kg, but only after repeated testing. Naloxone (0.1 and 1 mg/kg) failed to reverse facilitation in a number of these subjects. In Experiment 3, animals receiving their daily injections of morphine were allowed to self-stimulate only at 3 h post-injection (when ICS facilitation is usually maximal), rather than at 1 h and 3 h post-injection. ICS facilitation was not observed, even with repeated testing. These data indicate that the facilitation of ICS by morphine is the outcome of a learned association between drug administration and the ICS procedure, rather than the invariable result of opiate receptor activation. Repeated exposure to morphine is required for the initial establishment of ICS enhancement, but the subsequent expression of this behavior is not directly related to opiate receptor activity.