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PubMed1982

The substrates for lateral hypothalamic and medial pre-frontal cortex self-stimulation have different refractory periods and show poor spatial summation.

Refractory periods of the substrates for lateral hypothalamic (LH) and medial pre-frontal cortex (MPFC) self-stimulation were behaviorally estimated. The beginning of recovery from refractoriness was estimated as the time at which recovery was 20% complete. In all 7 rats, this estimate differed substantially across sites, averaging 0.66 msec and 1.59 msec for the LH and MPFC substrates, respectively. The recovery of excitability approached asymptote later in the MPFC substrate (3.5 msec) than in the LH substrate (1.5 msec). These findings are consistent with the view that different fibers subserve the reinforcing consequences of LH and MPFC stimulation. This notion is strengthened by the observation that the rewarding effects of stimulation summated poorly when stimulating pulses were concurrently delivered to these two sites.

Animals↗
PubMed1976

Amphetamine, chlorpromazine and clonidine effects on self-stimulation in caudate or hypothalamus of the squirrel monkey.

In 2 separate groups of squirrel monkeys and within 3 animals low rates of intracranial self-stimulation (ICSS) elicited from caudate or lateral hypothalamic brain sites were increased by as much as 200% above control levels by amphetamine (0.5 mg/kg). Thresholds for responding were decreased by 50%. Increasing the drug dose from 2 to 10 mg/kg produced response inhibition at both brain sites. The duration of inhibitory action of amphetamine (2.0 mg/kg) on ICSS from the medial forebrain bundle (MFB) area of the lateral hypothalamus was 6 hr. At caudate sites ICSS did not occur until 48 hr had elapsed. A 10 mg/kg dose of amphetamine produced a duration of actine of 36 hr in the MFB and 84 hr in the caudate. Chlorpromazine (CPZ) doses of 0.5 and 1.0 mg/kg decreased caudate ICSS significantly more than lateral hypothalamic ICSS. At 1.0 mg/kg the duration of action of CPZ was 6 hr at lateral hypothalamic brain sites and 24 hr at caudate sites. At a 2.0 mg/kg CPZ dose the duration of action was 12 hr in the MFB and 36 hr in the caudate. A dose of 0.10 mg/kg of clonidine blocked high rates of MFB ICSS while within the same animal caudate ICSS was much less affected. Higher doses (0.25 mg/kg) sedated the animal and ICSS was equally inhibited at both sites. These findings, using ICSS as a behavioral measure, suggest that the effects of amphetamine and CPZ involve not only hypothalamic structures but more anterior telencephalic sites as well. The prolonged actions of amphetamine and CPZ on caudate ICSS suggest that drugs acting, in part, on dopamine containing neurons will interfere with certain caudate mediated behavior. Further, since hypothalamic but not caudate ICSS sites are more dose sensitive to drugs that selectively act on NE containing neurons, other amines in addition to NE may play a role in the support of ICSS.

Amphetamine↗
PubMed1993

Intracranial self-stimulation and locomotor traces as indicators for evaluating the homopantothenic acid.

Our paper compares the effect of homopantothenic acid (HOPA) and haloperidol (HAL), i.e., representative neuroleptics, on intracranial self-stimulation (ICSS) and locomotor activity. These experiments showed that HOPA inhibited abnormal hyperactivity induced by methamphetamine (MAP) but did not inhibit ICSS which is considered with respect to physiological motivations. On the other hand, haloperidol (HAL) markedly inhibited both ICSS and abnormal hyperactivity induced by MAP. We propose that combined ICSS and locomotor traces can be chosen as indicators for evaluation and developing the new neuroleptics.

Animals↗
PubMed1982

Time course analysis of para-chlorophenylalanine induced suppression of self-stimulation behavior.

The hypothesis of a serotonergic basis of reward rests partly on data showing that serotonin (5-HT) depletion by para-chlorophenylalanine (p-CPA) causes depression of self-stimulation (SS) rates. These data do not clearly demonstrate a time course relationship between 5-HT depletion and SS suppression. The present study shows that SS behavior has fully recovered from p-CPA induced suppression when 5-HT levels are still maximally depleted. The data reveal that the effects of electrical brain SS on p-CPA induced reductions of 5-HT cannot explain the temporal dissociation between 5-HT depletion and SS suppression. As a whole the data suggest that midbrain 5-HT neurons are not critically involved in SS behavior.

Animals↗
PubMed1988

An analysis of the effects of amphetamine on brain self-stimulation behavior.

Rats were implanted with stimulating electrodes in the medial forebrain bundle-lateral hypothalamus, and trained in one of two brain self-stimulation (ICSS) procedures. One group of animals was trained in the auto-titration procedure which measured response rates and reinforcement thresholds for ICSS. When trained, the animals were tested with D-amphetamine (0.03-1.0 mg/kg) and saline. The second group of animals was trained in a procedure which established the discriminative properties of brain stimulation and which also measured the detection threshold for ICSS. When trained, the animals were tested with D-amphetamine and saline, and were subsequently tested with amphetamine and saline in an activity monitor. A graded decrease in mean reinforcement thresholds was produced by D-amphetamine. The two lower doses (0.03, 0.10 mg/kg) increased the rate of lever-pressing, but the highest dose (1.0 mg/kg) decreased it. No reliable changes in detection threshold occurred, although at the 0.3 mg/kg dose reductions were seen in two of five animals. Animals also showed a graded increase in motor activity with dose as well as increases in several performance measures. These results demonstrated that although amphetamine lowers reinforcement thresholds, it does not reliably alter detection thresholds, suggesting that the motivation to respond for ICSS is changed without any corresponding changes in the capacity to detect the presence of the stimulus.

Animals↗
PubMed1999

Effects of abused drugs on thresholds and breaking points of intracranial self-stimulation in rats.

The present study aimed to compare the effects of various abused drugs on threshold current intensities and the breaking points of intracranial self-stimulation. Effects of morphine (1-10 mg/kg, s.c.), d-amphetamine (0.3-3.2 mg/kg, i.p.), nicotine (0.1-3.2 mg/kg, s.c.), ethanol (0.6-2.4 g/kg, p.o.), caffeine (1-20 mg/kg, i.p.) and phencyclidine (0.3-5.6 mg/kg, i.p.) were studied in male Wistar rats trained to lever-press for electrical stimulation of ventral tegmental area. Morphine and d-amphetamine were the only two drugs that both decreased threshold currents and increased the maximal ratio of reinforced and non-reinforced responses. Nicotine (1 mg/kg) and ethanol (1.2 g/kg) lowered threshold currents while both decreases and increases in threshold current were seen after administration of low (5 mg/kg) and high (20 mg/kg) doses of caffeine, respectively. Nicotine, ethanol and caffeine had no effects in the progressive ratio procedure. Effects of phencyclidine did not reach levels of statistical significance in either procedure although high doses of phencyclidine disrupted performance in the progressive ratio procedure.

Animals↗
PubMed1994

Intracranial self-stimulation and locomotor traces as indicators for evaluating and developing antipsychotic drugs.

When chlorpromazine (CPZ) and lithium chloride (LiCl) are compared, the former suppresses both rat's intracranial self-stimulation (ICSS) and methamphetamine (MAP)-induced hyperactivity. On the other hand, the latter suppresses only MAP-induced abnormal hyperactivity but hardly suppresses a purpose-oriented ICSS associated with the reward system. Therefore, LiCl inhibits abnormal hyperactivity induced by MAP, but it does not suppress physiological motivation. Using the two types of antipsychotic drugs, the authors propose a method of combining the ICSS and locomotor activity together with its traces. These proposals are useful indicators for evaluating and developing the new antipsychotic drugs which are used clinically for psychotic patients and for understanding the drug-induced akinesia and anhedonia.

Animals↗
PubMed1996

Peptidase inhibitors potentiate the effects of neurotensin and neuromedin N on self-stimulation of the medial prefrontal cortex.

The purpose of this study was to examine the possible role of endogenous peptidases in the inhibition of intracranial self-stimulation (ICSS) produced by injections of neurotensin (NT) and neuromedin N (NN) into the medial prefrontal cortex (MPC) of the rat. We studied the effects on ICSS of the MPC of the administration of thiorphan and bestatin, two specific inhibitors of the peptidases that inactivate NT and NN respectively. Microinjections into MPC of thiorphan (10 micrograms) and bestatin (25 micrograms) potentiated in inhibition of ICSS produced by the intracortical administration of NT (10 nmol) and NN (20 nmol) respectively. This potentiation affected both the amplitude and the duration of the inhibition of ICSS produced by the neuropeptides. Our data indicate that endogenous peptidases are involved in the inactivation of NT and NN in the prefrontal cortex.

Animals↗
PubMed1990

Comparative assessment of pedal pressing rates of self-stimulation of hypothalamus and midbrain with both square wave and sine wave stimulus parameters.

In Wistar rats, the regional differences of pedal pressing rates of self-stimulation (SS) of lateral hypothalamus (LH) and substantia nigra-ventral tegmental area (SN-VTA) were assessed with electrodes implanted in both regions in each subject. Average of SS rates of SN-VTA sites was significantly higher than that of LH sites, tested with both sine wave and square wave types of stimuli. There was no significant difference in SS rates between males and females, and also in the females between different days of oestrus cycles. The high rates of robust SS observed in this study relative to SS rates reported in past literature were probably due not only to the placements of electrodes in the main substrates of SS, but also to the parameters of stimulus used (0.25 sec trains of sine waves through bipolar electrodes).

Animals↗
PubMed1982

Conditioned suppression of medial forebrain bundle and septal intracranial self-stimulation in the rat: evidence for a fear-relief mechanism of the septum.

A conditioned emotional response (CER) paradigm was presented to two groups of rats during intracranial self-stimulation (ICSS). One group bar pressed for medial forebrain bundle (MFB) stimulation reward; the other group bar pressed for septal stimulation reward. The MFB ICSS was found to be suppressed by the CER procedure, but this procedure failed to suppress septal ICSS. This difference between the two sites was found only when both MFB and septal ICSS current intensities were available at their optimal levels. When ICSS current intensities were lowered to either threshold or medium level, both groups exhibited the CER suppression effect. The animals were also tested for a possible analgesic effect produced by the ICSS. The MFB stimulation was found to produce some degree of analgesia, but septal stimulation failed to produce any analgesic effect. Thus, the possibility that the attenuation of the CER suppression effect in the septal group was due to analgesia was excluded. The difference in MFB and septal ICSS behavior during the presentation of the aversive stimulus suggested a possible qualitative distinction between the reward functions of these two sites, and a possible fear-reduction property of the septal area.

Animals↗
PubMed1987

Handling facilitates the acquisition of lever-pressing for brain self-stimulation in the posterior hypothalamus of rats.

Adult male rats implanted with stimulating electrodes in the posterior hypothalamus-ventral tegmental area (PH-VTA) were allowed to learn to lever press for intracranial self-stimulation (ICSS) without any priming by the experimenter or use of external cues. Animals that had been handled for seven days prior to testing acquired the lever-pressing task more rapidly than non-handled animals. Prior handling had no effect on the amount of locomotor activity in a novel environment nor on the number of non-reinforced lever presses. This suggested that the effect of handling on ICSS acquisition was not due to a change in locomotor activity or exploratory behavior. Implanted rats that were injected before each session with d-amphetamine (0.25 mg/kg) or saline did not differ in their rates of acquisition of ICSS in PH-VTA. However, injected animals acquired ICSS more slowly than the non-injected (handled and non-handled) animals. These results suggest that mild stressors applied before acquisition testing can alter the rate of learning of an operant task for ICSS in the posterior hypothalamic region and that small routine manipulations of animals can affect learning in operant training situations.

Amphetamine↗
PubMed1981

Increased intracranial self-stimulation in rats after long-term administration of desipramine.

The effects of long- and short-term administration of the tricyclic antidepressant desipramine on intracranial self-stimulation in rats were studied with electrodes in the A10 region of the dopamine-containing cell bodies of the ventromedial tegmentum. Long-term desipramine administration resulted in a significant shift to the left in the ascending portion of the rate--current intensity function, indicating that the activity of the mesolimbic dopamine system was enhanced. These findings point to a possible dopaminergic mechanism of action of antidepressants and support speculations concerning the role of dopamine-containing neurons in the pathophysiology of depression.

Animals↗
PubMedDate not supplied

[Effect of deprivation of the "rapid" phase of sleep on self stimulation of the hypothalamus and septum in white rats].

26 rats with bipolar electrodes in lateral hypothalamic and septal areas were learned to press the bar for electrical stimulation of the brain (monopolar square pulses, 0.1 msec, 100 cps, train length 250 msec). After stabilization of self-stimulation (SS) responses, the animals were deprived of rapid eye movement sleep (REM) for up to 4 days by confinement to a small platform surrounded by water. The rats were allowed to SS for 40 min per day during and after REM deprivation up to 1 month. It was found that REM deprivation strongly increased hypothalamic SS rates but failed to change SS thresholds. As to the septal SS, its rate either increased, with threshold unchanged or lowered (1st type), or remained steady (2nd type), or decreased, with threshold unchanged or risen. In most cases the deprivation led to alteration in the shape of SS rate/intensity curve, which remained during the whole experimental period (1 month).

Animals↗
PubMed1978

Modulation of intracranial self-stimulation behaviour by local perfusions of dopamine, noradrenaline and serotonin within the caudate nucleus and nucleus accumbens.

In order to examine the possible role of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in the control of intracranial self-stimulation behaviour (ICSS) a push-pull perfusion system was used to administer different consecutive doses of DA, NA and 5-HT to discrete regions within the caudate nucleus (CN) and nucleus accumbens (NAC) of rats during ICSS. Electrode placements supporting ICSS were in both the medial forebrain bundle (MFB) and the ventral mesencephalic tegmentum (VMT). Animals were allowed to determine the ICSS pulse train duration thereby permitting three measures of ICSS behaviour: (1) mean presses/min; (2) mean duration/press and (3) mean time pressed/min. Eleven electrode/cannula combinations were found to be responsive to both DA and 5-HT. The DA response profile was typified by a significant increase in mean presses/min, a significant decrease in mean duration/press and no significant change in the mean time pressed/min. The response profile for 5-HT was the converse of the DA pattern for the first two measures of ICSS, however, again there was no significant change in the mean time pressed/min. In addition, 8 electrode/cannula combinations were sensitive to NA; for 5 combinations the response pattern was similar to that of DA, however, the changes in ICSS were generally larger and of longer duration. For the remaining 3 combinations sensitive to NA there was no major change in mean presses/min but a dramatic increase in the mean duration/press and consequently, an increase in the mean time pressed/min. It is suggested that the central control of ICSS behaviour might depend, in part, upon a relative balance between DA and 5-HT systems within the CN and NAC. The operational characteristics of this balance may be subject to additional modulation by the activation of an adrenergic receptor.

Animals↗
PubMed1998

A search for the metabolic signal that sensitizes lateral hypothalamic self-stimulation in food-restricted rats.

Food deprivation and restriction increase the rewarding potency of food, drugs of abuse, and electrical brain stimulation. Based on evidence that the rewarding effects of these stimuli are mediated by the same neuronal circuitry, lateral hypothalamic self-stimulation (LHSS) was used to investigate the involvement of various metabolic signals in the sensitization of reward. In Experiment 1, glucoprivation with 2-deoxy-d-glucose (150 mg/kg, intraperitoneally (i.p.)) and lipoprivation with nicotinic acid (150 mg/kg, subcutaneously (s.c.)), individually and in combination, failed to affect the LHSS threshold in ad lib.-fed rats. These results suggest that signals associated with acute shortage of metabolic substrate do not sensitize reward. Because numerous responses to more prolonged negative energy balance are mediated by neuropeptide Y (NPY), the effect of exogenous neuropeptide Y upon LHSS was investigated in Experiment 2. Intraventricular infusion of orexigenic neuropeptide Y doses (2.0, 5.0, and 12.5 g), in ad lib.-fed rats, had no effect on LHSS threshold. In Experiment 3, other concomitants of prolonged negative energy balance--high circulating levels of free fatty acids (FFA) and beta-hydroxybutyrate (HDB)-were investigated. Nicotinic acid (250 mg/kg, s.c.), which suppressed serum HDB and FFA levels, had no effect on LHSS in food-restricted or ad lib.-fed rats. Mercaptoacetate (68.4 mg/kg, i.p.), which suppressed serum HDB levels and exacerbated the elevation of FFA levels, also had no effect. Thus, the brain reward system, if modulated by these substances, is not affected by transient, though marked, changes in their levels. To investigate the effect of a sustained increase in levels of FFA and HDB, a "ketogenic" diet was employed. Although this diet produced a fourfold increase in serum HDB levels, it had no effect on LHSS thresholds. Moreover, the failure of mercaptoacetate (68.4 mg/kg, i.p.) to decrease LHSS thresholds in these rats supports the conclusion that acute shortage of metabolic substrate does not sensitize reward. Other possible mechanisms of reward sensitization, including sustained decreases in circulating insulin and leptin and increases in corticosterone, are discussed.

Animals↗
PubMed1980

[Intracranial self-stimulation of the nucleus accumbens of the rat and its associated behavior (author's transl)].

In recent years, the nucleus accumbens (NAS) has gained prominence because of an interest in the role of catecholamine in the intracranial self-stimulation (ICSS). The NAS receives strong projections from dopamine of the ventral tegmemtal area (VTA) which form the meso-limbic dopamine pathway (A10). The major purpose of the present study was to investigate the ICSS of NAS with special emphasis on its associated behavior. The results obtained were as follows: 1. ICSS was observed in rats with electrodes in the NAS. The rate of its ICSS was 230 +/- 142/15 min. 2. Antidromic spikes (AS) in the VTA were observed with stimulation of NAS including stimulation of sites associated with ICSS. The latency of AS was 25.5 +/- 4.3 msec. (range 10.0-42.0 msec). 3. ICSS of NAS was chiefly associated with "approach-escape" behavior and/or sniffing for which its electrodes were observed to distribute on widespread scatter through NAS. The electrodes of digging and/or licking groups were localized historogically in the vicinity of the commissura anterior.

Animals↗
PubMed1980

Effect of clonidine and phentolamine on self-stimulation behavior in the dorsal and ventral regions of the lateral hypothalamus in mice.

The effects of IP injections of increasing doses of clonidine and phentolamine on self-stimulation behavior (ICSS) in the dorsal and ventral regions of the lateral hypothalamus were studied in C57BL/6 mice. Clonidine specifically stimulates alpha-noradernergic receptors and has two distinct effects on ICSS. Ventral hypothalamic ICSS is immediately depressed at low doses (5 microgram/kg) whereas dorsal ICSS exhibits a discrete increase. At higher doses, ICSS is perturbed at both sites. Phentolamine is a specific blocking agent of alpha-noradrenergic receptors and depresses dorsal ICSS more than that of the ventral region. These observations clearly indicate a noradrenergic influence in the dorsal region of the hypothalamus.

Animals↗