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At least 703 records · Page 39Linked to original sources
PubMed1980

Effects of an ACTH 4--9 related peptide upon intracranial self stimulation and general activity in the rat.

Adult male Sprague-Dawley rats were stereotactically implanted with electrodes within the anterior medial forebrain bundle. The rats were trained to respond for intracranial self-stimulation (ICS) and treated with control solution or varying doses of an ACTH 4--9 related synthetic peptide (Org 2766; H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH). The drug affected ICS as measured in overnight response records, with the highest dose reliably increasing the amount of responding. In a second experiment rats were similarly treated and general activity was assessed. No remarkable changes in activity were present at any tested dose. The findings corroborate previous reports suggesting ACTH-related peptides may be active in a variety of motivated tasks, but less active with respect to general activity.

Adrenocorticotropic Hormone↗
PubMed1981

Post-amphetamine depression of self-stimulation behavior in rats: prophylactic effects of lithium.

Rats reliably interrupted a photobeam for electrical brain stimulation when electrodes were situated in the substantia nigra. The reinforcing value of electrical brain stimulation diminished, markedly, when animals were exposed to long-term amphetamine treatment and then tested in the absence of the drug. Chronic lithium treatment administered in conjunction with amphetamine protected against the development of the post-amphetamine depression of self-stimulation responding. These findings were not related to drug-induced changes in locomotor activity.

Animals↗
PubMed2004

Corticospinal excitability during painful self-stimulation in humans: a transcranial magnetic stimulation study.

We investigated changes in the corticospinal pattern of activity in healthy volunteers during sustained noxious and non-noxious mechanical stimulation of the first hand digit, resulting from active (self-stimulation) or passive (externally-induced) pressing against a sharp or blunted tip. The results indicate that, in order to press a finger onto a noxious stimulus with the same force generated to press onto a non-noxious one, the motor cortex adopts a peculiar strategy in terms of recruitment of motor units. This is reflected by an increase of corticospinal excitability (as revealed by motor potentials evoked by transcranial magnetic stimulation of the contralateral primary motor cortex) and EMG activity of agonist muscles, possibly related to an increase of motor unit synchronization.

Adult↗
PubMed1988

Competition between lever-pressing behavior and thermoregulatory behavior on exposure to heat in intracranial self-stimulating rats.

To investigate the relationship between the thermoregulatory system and the brain-reward system, we examined effects of heat exposure and tail amputation on lever-pressing behavior in intracranial self-stimulating rats. Rats that continuously pressed a lever voluntarily for 1 hour at an ambient temperature (Ta) of 22 degrees C interrupted lever pressing and showed heat loss behaviors, such as grooming and body extension, at a Ta of 36 degrees C. Hypothalamic temperature (Thy) at the time of the first body extension was higher than that after 1 hour of lever-pressing at a Ta of 22 degrees C. Tail amputation experiments showed the same result. Thy at the onset of the body extension after tail amputation was higher than that at the end of 1 hour of lever-pressing under control conditions. The data suggest that thermal factors, especially Thy, are important in the control of lever-pressing behavior.

Amputation, Surgical↗
PubMed2000

Intracranial self-stimulation increases differentially in vivo hydroxylation of tyrosine but similarly in vivo hydroxylation of tryptophan in rat medial prefrontal cortex, nucleus accumbens and striatum.

We have examined using microdialysis the effect of intracranial self-stimulation (ICSS) on the in vivo hydroxylation rate of tyrosine and tryptophan in the medial prefrontal cortex (mPFC), nucleus accumbens (NAC) and striatum (STR). A decarboxylase inhibitor NSD-1015 was included in the perfusate, which enabled the simultaneous measurement of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) as an index of the in vivo hydroxylation level of tyrosine and tryptophan. When rats were exposed to 1 h of ICSS at the medial forebrain bundle (MFB), their extracellular levels of DOPA significantly increased in the mPFC, NAC and STR, but with a different magnitude and time course. The same stimulation produced a delayed increase in extracellular 5-HTP, compared to DOPA, in these brain regions. The profile of 5-HTP response demonstrated no apparent difference among the regions. These findings indicate that ICSS of the MFB can increase differentially the in vivo hydroxylation of tyrosine but similarly the in vivo hydroxylation of tryptophan in the mPFC, NAC and STR.

5-Hydroxytryptophan↗
PubMed1991

Intracranial self-stimulation motivates weight-lifting exercise in rats.

The purpose of this study was to determine the feasibility of using a positive reinforcement protocol to motivate weight-lifting exercise in rats. Intracranial self-stimulation was used to induce weight-lifting exercise. Bipolar electrodes were implanted in the ventral tegmental area of rats, and the animals were trained to bar press on a continuous reinforcement schedule for electrical brain stimulation. Animals with response rates of 1,200-1,500 presses/h were then trained with a discriminative light stimulus to alternate between a normally positioned bar and an elevated bar that could be reached only by standing on the hindlimbs. The animals were fitted with a weighted jacket at a starting resistance of 5-10% of their body weight. Weight-training sessions were conducted 5 days/wk for 10 wk. Training consisted of 600 presses/session, alternating every 15 presses between the low and high bars. At the beginning of each subsequent week, the resistance was progressively increased, with some animals eventually training at resistances greater than 50% of their body weight. At the end of the training period, the rats were lifting over 550% of the starting weight. Gastrocnemius size and mean fiber diameter were increased in the weight-lifting animals. This model combines exercise with positive incentive and has the advantages of being relatively easy to implement and not producing any apparent physical or mental trauma in the animal.

Animals↗
PubMedDate not supplied

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

A study has been made of the influence of disulphiram--a drug that lowers the level of norepinephrine and DOPA which restores its content in brain tissues,--on motivational and reinforcing effects caused by the action of a gradually increasing current on the self-stimulation (SS) zones. It has been shown that disulphiram, while suppressing motivational reactions does not exert such an effect on SS reactions. A half of the studied animals showed in these conditions an increased SS frequency. During disulphiram action (on the second day) DOPA restored motivational reactions and inhibited SS reactions. It is assumed that norepinephrine is involved in the mediatory system activating goal-directed motivational behaviour, but it does not constitute, as it seems, the major mediator of the reinforcement system.

Animals↗
PubMed2004

A progressive ratio schedule of self-stimulation testing in rats reveals profound augmentation of d-amphetamine reward by food restriction but no effect of a "sensitizing" regimen of d-amphetamine.

RATIONALE: Prior research indicates that psychostimulant-induced sensitization is not expressed in lateral hypothalamic electrical self-stimulation (LHSS)-based measures of drug reward, although the augmenting effect of chronic food restriction is. Neuroadaptations within the brain dopamine system have been identified in both psychostimulant-sensitized and food-restricted animals. Consequently, a variant of the LHSS paradigm in which responding is particularly sensitive to changes in dopaminergic tone may be best suited to detect and compare effects of chronic d-amphetamine and food restriction. Instrumental responding on a progressive ratio (PR) schedule is more sensitive to dopaminergic manipulations than is responding on a continuous reinforcement (CRF) schedule, but has not previously been used to examine chronic psychostimulant and food restriction effects on LHSS-based measures of drug reward. OBJECTIVE: The first aim of this study was to determine whether a regimen of d-amphetamine treatment, that produces locomotor sensitization (5 mg/kg per day x5 days), increases the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The second aim, was to determine whether chronic food restriction produces a marked increase in the reward-potentiating effect of d-amphetamine in the PR LHSS protocol and, if so, whether it is reversible in parallel with body weight recovery when free feeding is restored. METHOD: Reward-potentiating effects of a challenge dose of d-amphetamine (0.25 mg/kg, IP) were measured in terms of the break point of LHSS responding on a PR schedule of reinforcement, in ad libitum fed and food-restricted rats. RESULTS: A regimen of d-amphetamine treatment that produced locomotor sensitization did not increase the break point for LHSS in the presence or absence of d-amphetamine. Chronic food restriction produced a marked increase in the break point-increasing effect of d-amphetamine (3-fold), which returned to baseline in parallel with body weight recovery over a 4-week period of restored free-feeding. CONCLUSIONS: A locomotor-sensitizing regimen of d-amphetamine treatment does not increase the rewarding effect of LH electrical stimulation or the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The augmenting effect of chronic food restriction on drug reward is mechanistically and functionally different from psychostimulant sensitization and may be controlled by signals associated with adipose depletion and repletion.

Animals↗
PubMed1992

Interactions between alcohol and nicotine on intracranial self-stimulation and locomotor activity in rats.

These studies were aimed at investigating interactions between alcohol and nicotine on operant behavior and on locomotor activity. Independent groups of rats with electrodes in the lateral hypothalamus were trained to lever press for intracranial self-stimulation (ICSS) on either a fixed-ratio 15 (FR 15), FR 30, fixed-interval 15-second (FI 15-s) or FI 30-s schedule of reinforcement. In the FI 15-s experiment, nicotine increased and alcohol decreased responding. This also happened in the FI 30-s experiment; however, when the two drugs were combined, an increase in lever pressing occurred which was greater than that produced by nicotine alone. Nicotine increased rates in the FR 15 schedule but, when combined with alcohol, did not reverse the decrease in rates produced by alcohol. In the FR 30 schedule, nicotine also increased response rates, but did not reverse the decrease produced by alcohol in this paradigm. A separate group of animals was tested in a locomotor activity apparatus following administration of nicotine, alcohol or their combination. Nicotine increased locomotor activity and alcohol depressed it. However, when 0.10 or 0.17 mg/kg nicotine was combined with 0.3 g/kg alcohol, an increase greater than that produced by nicotine alone occurred. We have found that alcohol and nicotine together can produce a potentiation of nicotine's stimulatory effects depending upon the dose and the requirements of the task.

Animals↗
PubMed2003

Psychoactive compounds and their antibodies: effect on self-stimulation of the lateral hypothalamus in morphinized rats.

We studied the effect of morphine hydrochloride, brain-specific S100 protein, and antibodies to morphine, S100 protein, and opiate mu-receptors in ultralow doses on self-stimulation of the lateral hypothalamus in morphinized rats. This reaction in morphine-withdrawn rats underwent specific changes after single administration of test preparations. Repeated treatment with preparations in the same dose equalized emotional homeostasis. This effect was especially pronounced after treatment with antibodies to morphine, S100 protein, and opiate mu-receptors. Our findings should be taken into account in developing methods for non-narcotic substitutive therapy of patients with morphine dependence.

Analgesics, Opioid↗
PubMed1980

Self-administration of D-Ala2-Met-enkephalinamide at hypothalamic self-stimulation sites.

The relationship between the action of enkephalin and the reinforcing action of electrical stimulation in the posterior lateral hypothalamus of the rat was studied with the self-administration approach. Adult male albino rats implanted with a combination cannula and stimulation electrode in hypothalamus were pretested for the reinforcing effects of electrical stimulation. Only subjects that self-stimulated at moderate to high rates were given self-administration tests. The chamber for the self-administration tests was fitted with one lever at each end of a rectangular plexiglass box. In a session, one lever was 'active', the other not. The active lever, if depressed, yielded 20 nl of CSF (artificial cerebrospinal fluid), or CSF in which one of the test substances was dissolved. Each subject was tested repeatedly for the reinforcing effects first of a control solution (CSF), then of D-Ala2-Met-enkephalin (DALA), a long-acting synthetic analogue of enkephalin, then of morphine, and then of opioids mixed with naltrexone or naloxone. Following these tests, the subjects were once again given self-stimulation tests to ascertain the functional integrity of the 'reward' system after the repeated self-administration tests. The results demonstrate that when the test solution was DALA instead of CSF the subjects pressed the active lever at a higher rate than for CSF, and they exhausted the supply more rapidly than for CSF. The rate on the active lever was also significantly higher than on the inactive lever. DALA at 1 and 5 microgram/microliter concentrations proved more reinforcing than at 0.1 microgram/microliter. Naltrexone did not block the reinforcing effect of DALA, whereas naloxone blocked DALA-induced reinforcement. These data extend the report of ventricular methionine-enkephalin positive reinforcement to DALA injected directly into the lateral hypothalamus.

Animals↗
PubMed1997

Facilitation of a distributed shuttle-box conditioning with posttraining intracranial self-stimulation in old rats.

Old Wistar rats (16-17 months) were trained in a two-way active avoidance task for 5 consecutive days (10 trials/day). Immediately after each training session a lateral hypothalamic intracranial self-stimulation session (ICSS group) or a sham-treatment session (Control group) was given to the animals. Long-term retention was tested 7 days after the last acquisition session. ICSS treatment led to a significant improvement in acquisition. In the long-term retention session the level of avoidance in both groups was similar to that achieved in the last acquisition session, although differences among groups failed to reach statistical significance. These results are compared with those obtained in previous experiments with young adult rats. While ICSS facilitated the process of acquisition in both young and old rats (however, it was much more powerful in young animals), further experiments are needed to elucidate whether this effect is long-lasting in old rats, as occurs in young adult subjects.

Animals↗
PubMed1979

Morphine and intracranial self-stimulation in the hypothalamus and dorsal brainstem: differential effects of dose, time and site.

The purpose of this study was to examine if morphine, a drug of abuse, exerts site-specific effects on intracranial self-stimulation (ICSS). Rats, implanted with dorsal brainstem (DB) and hypothalamic (HYP) electrodes, bar-pressed for ICSS at two current intensities eight hours a day during six days each of predrug saline, morphine (2.5, 5.0, 7.5 or 10.0 mg/kg) and postdrug saline conditions. There were three patterns of drug effects: "pure" depressions, "pure" facilitations and a biphasic pattern (depressions followed by facilitations). Repeated morphine administration modified the temporal patterning of these effects: shortened duration of depressions and produced earlier onsets of facilitations. Within an animal, DB electrodes displayed more depressions than the HYP electrodes. Tolerance to the depressant effects, observed frequently, occurred occasionally to the facilitative effects of morphine. The drug effects on ICSS were dissociated from those observed on other behavioral measures, and thus are not artifacts of concomitant changes in activity levels.

Animals↗
PubMedDate not supplied

[Effects of antidepressants in models of brain self-stimulation and place preference after prolong social isolation and alcoholization].

In rats rearing in social isolation since 17th day of life and treated with 5-15% ethanol solution within 3 months, the effects of antidepressants on self-stimulation of lateral hypothalamus and place preference were studied. The comparative study of seven antidepressants with different mechanism of action (fluoxetine, maprotiline, tianaptine, pyrazidol, sertraline, citalopram, mianserin) was shown that pyrazidol and tianeptine and in a less degree sertraline and citalopram possessed the significant antidepressant activity in the model of social isolation and maprotiline and tianeptine did in model of alcoholization. It is concluded that antidepressants studied activate the reinforcing properties of the brain, that is associated with the involvement of both the catecholamine and serotonin system, working reciprocally.

Animals↗
PubMed1999

Control of motor seizures by brotizolam with maintenance of stable refractory periods for self-stimulation.

In recent years, we have been pursuing our mapping investigations of the substrate for brain-stimulation reward in regions of the anterior hypothalamic and lateral preoptic areas. However, one problem is that stimulation of these sites often generates overt seizures so that their suppression via a pharmacological means would be very useful. The sedative-hypnotic benzodiazepine, brotizolam, is reportedly a long-lasting anticonvulsant. Hence, its effects on motor seizures elicited from stimulation of the lateral preoptic area were evaluated in the first experiment. Both tested doses (5.0 and 7.5 mg/kg) of the drug were shown to significantly decrease the number, and marginally, the severity of stimulation-induced seizures; furthermore, this effect was relatively long lasting, up to about 3 h. The higher dose of brotizolam did not alter the single-pulse thresholds for self-stimulation, a requirement for evaluations of poststimulation excitability, the purpose of the second experiment. Here, our interest was in documenting whether the membrane properties of the stimulated neurons, as assessed by refractory periods, were altered by brotizolam. No differences in the time course of recovery were observed; refractoriness began between 0.4 and 0.8 ms, and reached 50% recovery by 2.0 ms, which is consistent with the pattern of poststimulation excitability typically measured at these sites. Thus, in addition to its long-lasting suppression of motor seizures in rats, brotizolam does not alter the time course of recovery from refractoriness of the neurons that mediate brain-stimulation reward in the lateral preoptic area.

Analysis of Variance↗
PubMed1994

4-Ethoxyamphetamine: effects on intracranial self-stimulation and in vitro uptake and release of 3H-dopamine and 3H-serotonin in the brains of rats.

Experiments were conducted to compare the effects of 4-ethoxyamphetamine, a novel "designer" amphetamine, with (+)-amphetamine and an earlier "designer" amphetamine, 4-methoxyamphetamine, on rats. (+)-Amphetamine significantly decreased frequency threshold measures in an intracranial self-stimulation (ICSS) procedure using medial forebrain bundle electrodes, while 4-methoxyamphetamine and 4-ethoxyamphetamine increased these ICSS frequency thresholds. 4-Methoxyamphetamine and 4-ethoxyamphetamine had more potent effects on inhibition of uptake and stimulation of spontaneous release of 5-hydroxytryptamine (serotonin) than of dopamine. It is concluded that the neuropsychopharmacological profile of 4-ethoxyamphetamine is unlike that of (+)-amphetamine, but similar to that of 4-methoxyamphetamine, a potent hallucinogen in humans.

Amphetamines↗
PubMed1976

[Effects of psychotropic drugs and the roles of the noradrenergic and dopaminergic systems in the lateral hypothalamic self-stimulation behavior].

A bipolar electrode was stereotaxically implanted in or near the medial forebrain bundle at the level of the posterior lateral hypothalamus of male albino Wistar-Imamichi rats. 1) Two electrode sites implanted in a rat both in the lateral hypothalamus and in the dorsal noradrenaline bundle supported self-stimulation (SS) behavior. 2) Methamphetamine facilitated the SS dose-dependently in the "threshold"-intensity reinforcement. The pretreatment of imipramine enhanced the effects of methamphetamine, but that of chlorpromazine inhibited those effects. Methamphetamine facilitated the SS also in the moderate-intensity reinforcement. Imipramine had no significant effects. On the other hand, chlorpromazine inhibited markedly the SS behavior. 3) FLA63 and U-14,624, dopamine beta-hydroxylase inhibitors, suppressed the SS behavior. Both drugs significantly reduced brain norepinephrine levels. FLA63 significantly increased the levels of dopamine, but the increase with U-14,624 was not significant. 4) Apomorphine, stimulant of dopamine receptor, did not facilitate, but rather suppressed the SS in the "threshold"-intensity reinforcement. 5) l-Norepinephrine injected into the lateral ventricle facilitated the rate of SS, dose-dependently. On the other hand, dopamine had no detectable effects. 7) These results suggest that the noradrenergic system in the brain plays a more important role in the positive reinforcement of the lateral hypothalamic SS behavior than does the dopaminergic system.

Animals↗