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At least 757 records · Page 42Linked to original sources
PubMed2005

Behavioral effects of intra-cranial self-stimulation in an animal model of attention-deficit/hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD), characterized by inappropriate levels of activity, attention, and impulsivity, has been suggested to be caused by changes in reinforcement and extinction processes possibly linked to dysfunctioning dopamine systems. The present study investigated reinforcement processes in spontaneously hypertensive rats (SHR), an animal model of ADHD. Using intra-cranial self-stimulation (ICSS), behavioral effects of varying current intensity, reinforcer density, and reinforcer delay were tested. Current was varied in order to find the weakest current producing the maximal response rate (optimal current) in the SHR and the controls during high (120 reinforcers/min) and low reinforcer densities (1 reinforcer/min). The results showed that optimal current was significantly lower in the SHR than in the controls during high reinforcer density while maximal response rates were not significantly different. During low reinforcer density, optimal current was not significantly different in the two strains, but maximal response rate was significantly higher in the SHR than in the controls. The SHR produced more responses during the testing of reinforcer density, but changes in reinforcer density affected response rates similarly in the two strains. The decrease in response rate as a function of reinforcer delay was more pronounced in the SHR than in the controls. Overall, more responses with short inter-response times (IRT) were found in the SHR compared to the controls during intermittent reinforcement. The results are consistent with a steepened delay-of-reinforcement gradient in SHR.

Analysis of Variance↗
PubMed2004

Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats.

RATIONALE: Elevations in cAMP response element binding protein (CREB) function within the mesolimbic system of rats reduce cocaine reward in place conditioning studies and increase immobility in the forced swim test. Each of these behavioral adaptations can be interpreted as a depressive-like effect (i.e., anhedonia, despair) that may reflect reduced activity of brain reward systems. Furthermore, each effect appears due to increases in CREB-mediated expression of dynorphin, since each is attenuated by intracranial injections of the kappa-opioid receptor antagonist norBNI. OBJECTIVES: Intracranial self-stimulation (ICSS) studies were conducted in rats to determine whether administration of a kappa-agonist would have depressive-like effects on brain stimulation reward, and whether pretreatment with a kappa-antagonist would attenuate any such effects. Conditions that have depressive effects in people (e.g., drug withdrawal) increase the threshold amounts of stimulation required to sustain ICSS in rats. METHODS: Sprague-Dawley rats with lateral hypothalamic stimulating electrodes were tested in a "curve-shift" variant of the ICSS procedure after systemic administration of the kappa-agonist U-69593 alone, the novel kappa-antagonist 5'-acetamidinoethylnaltrindole (ANTI) alone, or co-administration of both drugs. RESULTS: U-69593 dose dependently increased ICSS thresholds, suggesting that activation of kappa-receptors reduced the rewarding impact of the brain stimulation. ANTI had no effects on its own, but it attenuated increases in ICSS thresholds caused by the agonist. CONCLUSIONS: These data provide further evidence that stimulation of brain kappa-receptors may trigger certain depressive-like signs, and that kappa antagonists may have efficacy as antidepressants without having reward-related actions of their own.

Animals↗
PubMedDate not supplied

[Effect of stimulation of the reticular formation on the motivational and reinforcing effects of the self stimulation zones].

The influence was studied on the midbrain reticular formation (RF) on motivational and reinforcing effects of stimulation of the same selfstimulation zones (SS) of hypothalamic area. A current of gradually increasing intensity was used, by means of which three groups of functionally (behaviourally) specific reticular points were revealed: motivationaly neutral, positive and negative. The data obtained show that influences of RF on SS zones of hypothalamus differand depend on functional properties of various RF areas. Changes of motivational effects in SS zones reflex the specificity of reticular foci in a lesser degree than changes in reinforcing effects. It has been suggested that reinforcing effects of the SS hypothalamic zones possess their own activating mechanism specifically related to its "positive" link and differing from reticular mechanism of unspecific activation.

Animals↗
PubMed1981

The role of dopamine in pontine intracranial self-stimulation: a re-examination of the problem.

Subsequent of their achieving stable rates of responding for electrical stimulation through electrodes implanted in the region of the brachium conjunctivum, rats were anaesthetized and 6-hydroxydopamine injected through an implanted guide tube into the area of lateral hypothalamus in which the ascending axons of dopamine-containing neurones are found. The resultant destruction of these axons had similar temporary effects on the behaviour of the animals whether it was ipsilateral or contralateral to the electrode. It is concluded that nigral or mesolimbic dopaminergic systems are not involved in pontine intracranial self-stimulation behaviour.

Animals↗
PubMed1983

Wheel-running of rats in combination with a simple self-stimulation procedure.

LONG EVANS hooded rats with chronically implanted electrodes in the Area hypothalamica lateralis (AHL, group 1), the Nucleus linearis rostralis (LR, group 2) and the Nucleus centralis superior (CES, group 3) were offered the possibility to spontaneously perform wheel-running for one hour per session. The number of wheel revolutions per ten minutes and per hour were counted automatically. The rats were connected with a square wave generator by a smooth flexible cable and received stimulus series (50 imp./s; 0.5 ms imp. duration; 0.5 s series duration; 0-3 V intensity) triggered by each complete revolution of the wheel. The sessions took always place at the same time of the day and under the same experimental conditions -- except the change of stimulus intensity. The results with 0 V served as controls. The method has the following advantages: 1. Self-stimulation is induced spontaneously in the first stimulation session. 2. Negative emotional effects can be quantified by the decrease of the wheelrunning activity. -- AHL stimulation caused an increase in the wheel-running activity amounting to 300-350% with a maximum at 3 V. LR stimulation brought about an ambivalent effect with increase to 200% at 1-2 V and decrease to 56% at 3 V. During CES stimulation an increase to 166-240% with its maximum at 2 V was observed. Stimulation with the same parameters did not evoked locomotion in an open field situation.

Animals↗
PubMed1989

Differential effects of cholinergic drugs on discriminative cues and self-stimulation produced by electrical stimulation of the ventral tegmental area.

Cholinergic receptors have been shown to modulate a subset of discriminative cues produced by electrical stimulation of the ventral tegmental area (VTA) in rats. The present study identified the specific cholinergic receptor type modulating these electrical brain-stimulation (EBS) cues, and assessed whether these receptors also mediated the rewarding effects of VTA EBS. The EBS cues were enhanced by the acetylcholinesterase inhibitor physostigmine and the muscarinic receptor agonists pilocarpine and RS-86, whereas the nicotinic receptor agonist nicotine had no effect. The enhancing effects of pilocarpine or RS-86 were attenuated by the muscarinic antagonist scopolamine. The EBS cues were not affected when scopolamine was injected alone, although high doses disrupted discriminated responses. Intracranial self-stimulation (ICSS) rates were depressed by physostigmine and pilocarpine and increased by nicotine and scopolamine. These results indicated a facilitatory influence of muscarinic receptors on the EBS cues, and an inhibitory role in VTA ICSS. Nicotinic receptor activation did not affect the EBS cues, but facilitated ICSS. These differential effects of cholinergic receptor activation point to a dissociation of the specific EBS cues measured in this study from the rewarding effects of VTA stimulation.

Animals↗
PubMed1980

External stimulus control of self-stimulation behavior.

Dogs with electrodes implanted in the anterior forebrain region were successfully trained to leverpress for brain stimulation reward upon the presentation of a 1000 Hz tonal conditioned stimulus and to withhold responding during its absence and upon a 2000 Hz tonal discriminative stimulus. The conditioned response extinguished upon removal of reward and was promptly restored when reward became again available. The results are discussed in terms of a conditioned drive induced by the action of the cue. It is proposed that environmental factors play an important role in the initiation and maintenance of self-stimulation behavior. Brain stimulation reward may serve as reinforcer of conditioned instrumental reflexes in an essentially similar way as natural rewards.

Animals↗
PubMed1969

Facilitation of brain self-stimulation by central administration of norepinephrine.

Rats with electrodes implanted in the medial forebrain bundle stimulated their own brains at sharply reduced rates after systemic administration of disulfiram or intraventricular administration of diethyldithiocarbamate. Both drugs inhibit dopamine-beta-hydroxylase, the enzyme responsible for the final step in the biosynthesis of norepinephrine. The suppressed behavior was reinstated by intraventricular injections of 1-norepinephrine, but not by injection of its biologically inactive isomer, d-norepinephrine. Intraventricular administration of dopamine and serotonin did not restore self-stimulation. The rewarding effect of medial forebrain bundle stimulation may depend on the availability of norepinephrine as a transmitter, but not on dopamine or serotonin.

Animals↗
PubMed1977

The cardiac self-stimulation hypothesis and the chick's differential attraction toward intermittent sound.

Two experiments were conducted to determine whether the chick's attraction toward specific rates of intermittent sound stems from long-term prehatch exposure by the chick to its own fetal heart beat. Contrary to prediction, Experiment I showed stronger attraction toward an intermittent square wave white noise signal matched for pulse rate, overall pulse duration, and mean intensity, than the sound of the actual fetal heart beat from which this attraction is said to derive, Experiment II demonstrated that long-term prehatch exposure to an intermittent auditory signal having a normally non-preferred rate will not establish an attraction for that same rate after hatching unless it contains a frequency component having latent appetitive properties. Alternatives to the cardiac self-stimulation hypothesis are discussed and, in the context of related evidence, the fetus' general capacity for exposure learning is reconsidered.

Acoustic Stimulation↗
PubMed1995

Median raphe injections of 8-OH-DPAT lower frequency thresholds for lateral hypothalamic self-stimulation.

The selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reduces the activity of brain 5-HT neurons via somatodendritic autoreceptors located in the midbrain raphe nuclei. This action of 8-OH-DPAT results in reduced 5-HT synthesis and release of 5-HT in terminal regions. Previous studies have shown that injecting 8-OH-DPAT into the raphe nuclei stimulates feeding, sexual behaviour, and locomotor activity, and serves as an unconditioned stimulus for inducing a conditioned place preference. This behavioural profile suggests that raphe injections of 8-OH-DPAT facilitate reward-related behaviour. The present study tested this hypothesis by investigating the effects of median raphe injections of 8-OH-DPAT on sensitivity to lateral hypothalamic (LH) self-stimulation. Frequencies required to sustain half-maximal rates of responding were determined following injection of saline or various doses of 8-OH-DPAT (0.2-5 micrograms) into the median raphe. In four rats with accurate injection sites 8-OH-DPAT dose-dependently lowered frequency thresholds by up to 40%. In the remaining rats injection sites were located outside the median raphe, and 8-OH-DPAT either slightly raised or failed to lower frequency thresholds. These results show that 8-OH-DPAT injected into the median raphe facilitates brain stimulation reward, and suggest that acute reductions in 5-HT neurotransmission may enhance sensitivity to rewarding stimuli. The possible interactions between 5-HT neurons and efferent systems utilizing dopamine and acetylcholine as neurotransmitters in mediating this effect are discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1975

Control of the rat's circadian self-stimulation rhythm by light-dark cycles.

Rats with hypothalamic and septal electrodes were maintained in continuous test environments where bar-press responses produced brief reinforcing electrical stimulations. Long-term trends in response emission were measured under continuous exposure to light, dark and 12 hr light-dark alternations. In addition, transient behavioral adjustment to sudden 180 degrees phase shifts in the light-dark schedule was studied. The ambient light condition was found to control the period and phase of the circadian rhythm of brain self-stimulation behavior, as quantified by Fourier analysis. The circadian period was greatest under constant light (up to 24.90 hr under dim illumination), and approximated 24.00 hr under constant dark. Successful nocturnal entrainment to 12 hr light-dark alternations was obtained, with the peak of the 24 hr Fourier fundamental occurring in the middle-to-late dark segments. Three to 11 days were required for re-entrainment to 180 degrees light-dark phase shifts, during which the behavioral oscillation period increased to values comparable to periods under constant light. The rate of re-entrainment appeared to be proportional to illumination intensity during light segments.

Animals↗
PubMedDate not supplied

Balance of glutamate and dopamine in the nucleus accumbens modulates self-stimulation behavior after injection of cholecystokinin and neurotensin in the rat brain.

Subpopulations of dopamine (DA) neurons in the ventral mesencephalon have been reported to contain cholecystokinin (CCK) and neurotensin (NT), giving rise to DA, DA/NT, NT/CCK and DA/CCK/NT projections. More precisely, colocalized DA/CCK neurons project mainly to the caudal part of the medial nucleus accumbens, whereas its rostral portion receives CCK and DA nerve terminal networks that are structurally independent. We investigated the respective effects of both CCK and NT on the intracranial self-stimulation behavior (ICSS) from the posterolateral hypothalamus after their direct administration into the lateral ventricle (ICV), into both portions of the nucleus accumbens, into the ventral tegmental area (VTA), and into the subiculum of the hippocampal formation (SUB). The ICV injection of 150 pmol CCK8 induced a decrease in the rate of ICSS. By contrast, the direct administration of 150 pmol CCK8 into the mediocaudal part of the nucleus accumbens induced an enhanced rate of ICSS while a similar injection into its rostral portion gave rise to a slight transient decrease of ICSS. When injected into the SUB, both CCK8 and glutamate produced decreased rates of ICSS at femtomolar doses one thousand-fold under the picomolar concentrations used for ICV injections. Neurotensin induced similar behavioral profiles to that observed after the ICV injection of CCK8 or into both portions of the nucleus accumbens. Neurotensin and CCK8 displayed opposite effects on ICSS when administered into the SUB or into the VTA, suggesting they may regulate ICSS most probably through different synaptic mechanisms and through different anatomical pathways.

Animals↗
PubMedDate not supplied

Afferent projections to the self-stimulation regions of the dorsal pons, including the locus coeruleus, in the rat as demonstrated by the horseradish peroxidase technique.

Afferent projections to the dorsal pons of the rat have been studied using the horseradish peroxidase (HRP) technique. HRP injections were made in each of the following regions: the vicinity of the locus coeruleus (LC); the periventricular gray, medial to the LC; the medial parabrachial region, lateral to the LC; the ventral cerebellum, dorsal to the LC; and the pontine reticular formation, ventral to the LC. Because intracranial self-stimulation (ICSS) has been obtained in these regions, the afferents have been discussed in terms of their possible contributions to the behavior. Previous ICSS studies of the dorsal pons have focussed on the LC as playing a central role. Presently identified inputs to the LC include: the dorsal raphe nucleus: the ventrolateral periaqueductal gray: the pontine reticular formation: the areas that contain the pontine and medullary noradrenergic and adrenergic cell groups: the lateral hypothalamic area: the contralateral LC: the deep cerebellar nuclei: the ventrolateral and parafascicular thalamic nuclei: and the parabrachial regions of the pons and midbrain.

Afferent Pathways↗
PubMed2005

The GABAB receptor-positive modulator GS39783 and the GABAB receptor agonist baclofen attenuate the reward-facilitating effects of cocaine: intracranial self-stimulation studies in the rat.

There is an increasing interest in the development of nondopaminergic pharmacotherapies for cocaine abuse. Emerging preclinical and clinical data with the metabotropic GABAB receptor agonist baclofen support a role for the modulation of GABAB receptors in the treatment of drug addiction. Nevertheless, the muscle relaxant, hypothermic, and sedative properties of baclofen somewhat limit its widespread potential therapeutic utility. Recently, positive modulators of the GABAB receptor such as GS39783 (N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine) have been identified. These positive modulators enhance the effects of GABA (gamma-aminobutyric acid) through actions at an allosteric site and are devoid of intrinsic agonistic efficacy. The aim of the present study was to assess the ability of the novel GABAB-positive modulator GS39873 or baclofen to modulate the behavioral effects of cocaine. Drugs of abuse such as cocaine lower brain reward thresholds obtained using intracranial self-stimulation (ICSS). We demonstrate here that GS39783 had no intrinsic effects on ICSS reward thresholds (10-100 mg/kg p.o.) in rats, whereas the full GABAB receptor agonist baclofen (2.5-5 mg/kg p.o.) dose dependently elevated thresholds. Moreover, both GS39783 and baclofen attenuated the threshold lowering effect of cocaine administration (10 mg/kg intraperitoneally) in a dose-related manner. These data strongly suggest that activation of GABAB receptors attenuates the rewarding effects of acute cocaine. Therefore, GABAB-positive modulation may represent a novel therapeutic strategy for the treatment of cocaine dependence and possibly other drugs of abuse without the side effects of full GABAB receptor agonists.

Analysis of Variance↗
PubMed2006

Role of alpha(1)-adrenoceptors of the locus coeruleus in self-stimulation of the medial forebrain bundle.

The present experiments were undertaken to clarify the role of central alpha(1)-adrenoceptors in reward processes. Rats, trained to self-stimulate via electrodes in the medial forebrain bundle of the lateral hypothalamus, were administered alpha(1)-selective drugs near the locus coeruleus (LC), a site of a dense concentration of alpha(1)-receptors. Effects on reward potency were assessed from shifts in rate-frequency curves while effects on motor response capacity were judged from changes in the maximal rates of responding. It was found that local blockade of LC alpha(1)-receptors with terazosin produced a significant dose-dependent and site-dependent rightward shift of 0.08 log units and a significant decrease of 16.3% in the maximum response rate. Both effects were completely reversed by coadministration of the alpha(1)-agonist, phenylephrine and were not attributable to terazosin's weak action at alpha(2)-adrenoceptors. It is concluded that LC alpha(1)-adrenoceptors are involved both in reward/motivational processes and operant response elaboration which are postulated to work together to facilitate goal attainment.

Adrenergic alpha-Agonists↗
PubMed1985

Self-stimulation of an 'aversive' brain structure: the mesencephalic central gray area.

Four experiments were performed in BALB/c mice implanted either in the lateral hypothalamus (LH) or in the dorsal part of the mesencephalic central gray area (CG) or both in LH and CG. In the first 3 experiments the animals were placed in a Y-maze where they could successively trigger and turn off continuous electrical stimulation. Expt. 1 showed that mice stimulated in CG (like animals stimulated in LH) are able to discriminate between the reinforced and the non-reinforced arm of the Y-maze in order to self-administer the stimulation. This behavior was observed whether the experimental situation was a simple spatial discrimination or a more complex light-dark discrimination. During the second experiment, the animals could choose between stimulation of low intensity (in one arm) or high intensity (in the other arm). We observed that, like LH animals, CG implanted mice chose the higher stimulation, despite its strong aversive component. On the other hand, Expt. 3 showed that when the animals could chose between CG stimulation, whose intensity was progressively increased, and LH stimulation whose intensity remained constant (low) they preferred the latter. When the mice were placed in a lever-press box where they could obtain 0.2 s of electrical stimulation (last experiment), LH animals showed vigorous self-stimulation behavior, whereas CG animals showed only a weak response rate. These results show that, in spite of its aversiveness, dorsal CG stimulation has an appetitive component whose magnitude may vary under different experimental conditions.

Animals↗