Behavioral measurement of the post-stimulation excitability of neurons mediating self-stimulation by varying the voltage of paired pulses.
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Animals↗
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Results for “SELF STIMULATION”
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Self-stimulation at the lateral hypothalamus and locus coeruleus after specific unilateral lesions of the dopamine system.
A group of rats was trained to press levers for electrical stimulation from bipolar electrodes aimed at the lateral hypothalamus (LH), and another group was trained to self-stimulate from electrodes in the locus coeruleus (LC). All rats in both groups were subjected to unilateral injections of 6-hydroxydopamine into the substantia nigra and midbrain ventral tegmentum. The lesions produced profound depletions of dopamine from the ipsilateral frontal cortex, nucleus accumbens/olfactory tubercle, and corpus striatum. Pretreatment with desmethylimipramine prevented loss of noradrenaline in excess of that caused by electrode implantation. The destruction of the dopamine projections produced a persistent and pronounced deficit in intracranial self-stimulation from ipsilateral electrodes in both the LH and LC groups, but only transient effects on self-stimulation from contralateral electrodes at these sites. These results suggest that an intact dopamine system is required for the expression of self-stimulation behaviour.
Animals↗
PHYSIOLOGICAL CONSEQUENCES OF BRAIN STIMULATION IN EXPERIMENTS ON INTRACRANIAL SELF-STIMULATION AND CONDITIONING WITH A NOTE ON PHYSIOLOGICAL RECORDING IN PSYCHIATRIC PATIENTS.
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Brain↗
Acetylcholine release in ventral tegmental area by hypothalamic self-stimulation, eating, and drinking.
Evidence is presented for an acetylcholine (ACh) input to the midbrain ventral tegmental area (VTA) as part of a system for self-stimulation and ingestive behavior. Male rats were prepared with an electrode in the perifornical lateral hypothalamus and an ipsilateral guideshaft for microdialysis in the VTA. Extracellular ACh increased in the VTA during self-stimulation, auto-stimulation, eating, or drinking. Infusion of atropine into the VTA via the microdialysis probe was sufficient to stop self-stimulation and reduce intake of food. It is concluded that ACh acts at muscarinic receptors in the VTA as part of a circuit that modulates hypothalamic self-stimulation and ingestive behavior.
Animals↗
Hypothalamic self-stimulation: the role of dopamine and possible relations to neocortical slow wave activity.
Reserpine abolishes self-stimulation in rats but the behavior can be restored temporarily by treatment with D-amphetamine or L-DOPA. Apomorphine does not restore self-stimulation even though it restores spontaneous motor activity in reserpinized rats. The data indicate that dopamine plays a role in reinforcement as well as in motor function. The ability of D-amphetamine to restore self-stimulation in reserpinized rats is eliminated by concurrent treatment with atropine or scopolamine. This effect may be related to the presence of continuous large amplitude slow wave activity in the neocortex under these conditions.
Animals↗
Lateralized attenuation of hypothalamic self-stimulation after injecting histamine synthesis blocker alpha-FMH into the E2 tuberomammillary subnucleus.
The tuberomammillary nucleus (TM), located in the posterior hypothalamic region, is the only known source of neuronal histamine. Unilateral lesions in the rostroventral part of this nucleus enhanced ipsihemispheric lateral hypothalamic self-stimulation behavior, suggesting that this region exerts inhibitory control over the neuronal systems related to reward or reinforcement processes. To examine whether the amplification of reinforcing stimulation following lesions of histamine synthesizing neurons is indeed histamine mediated, we blocked histamine synthesis unilaterally by injection of 200 microg alpha-fluoromethylhistidine into the E2 region of the TM, and assessed the effects on electrical self-stimulation behavior in the lateral hypothalamus (LH) of rats. Based on the finding that TM lesions facilitated such self-stimulation behavior, we hypothesized that this treatment would have similar effects. Unexpectedly, there was a sharp decrease in the rate of ipsihemispheric lateral hypothalamic self-stimulation following the injection of alpha-FMH compared to the contralateral hemisphere of treated animals as well as compared to the vehicle group. Response rates were most strikingly attenuated 1 h postinjection, but remained low over the whole 7 days of testing. Opposite behavioral effects of TM lesions and alpha-FMH application have been reported previously, and the effectiveness of alpha-FMH in reducing brain histamine levels is known to differ between brain regions. The fact that the alpha-FMH injection affected self-stimulation only in the ipsilateral hemisphere rules out an interpretation of the results in terms of unspecific effects of the treatment on arousal and other performance variables, and, instead, indicates a functional interaction with a subsystem linked to lateral hypothalamic reinforcement processes.
Animals↗
[Changes in the pattern of hippocampal neuron discharge as a reflection of the reinforcement effect in self-stimulation].
Changes of the unit activity patterns occurred in the rabbit dorsal hippocampus after self-stimulation. The changes occurred mostly in the theta-burst neurons and in neurons with reduction of spike amplitudes within each burst of discharges. Spontaneous activity of these neurons revealed bimodal histograms of interspike interval distribution. Within 1--3 sec after the self-stimulation the burst-type activity transformed into the regular or arrhythmic one with monomodal form of histogram. Spontaneously regular and arrhythmic neurons revealed no change of patterns. The findings corroborate the Grshtian hypothesis that the reward effect in self-stimulation is correlated with the motor rebound-effect. Experiments with cessation of reinforcing stimulus suggested a dependence of the burst-type pattern of discharges of the hippocampal neurons on the functional state of expectancy of the reinforcing stimulus.
Animals↗
Acidic Amino Acids and Self-stimulation of the Prefrontal Cortex in the Rat: A Pharmacological Study.
The effects of intraventricular and intracortical microinjections of acidic amino acid antagonists on self-stimulation (SS) of the medial prefrontal cortex (MPC) were investigated. Self-stimulation was measured by depressing a lever in a standard chamber. Spontaneous motor activity of the animal and SS of the contralateral non-injected MPC were used as control for non-specific effects of the drugs. Intraventricular microinjections of gamma-d-glutamylglycine (DGG), an antagonist of NMDA, kainate and quisqualate receptors, or 2-amino-5-phosphonovalerate (AP-5), a specific antagonist of NMDA receptors, produced a dose-related decrease of SS in the MPC. Spontaneous motor activity of the animal was not significantly affected. Unilateral microinjections into the medial prefrontal cortex of DGG or AP-5 produced a decrease of SS in the ipsilateral side while no effects were found on the contralateral MPC. On the contrary, intraventricular microinjections of gamma-d-glutamyltaurine (Glu-tau), an antagonist with more relative affinity for kainate and quisqualate receptors, produced a dose-related decrease of both self-stimulation and spontaneous motor activity of the rats. Moreover, intracortical microinjections of Glu-tau had no effect on self-stimulation of this cortical area. These results suggest that acidic amino acids through NMDA, but not kainate or quisqualate, receptors could be part of the neurochemical substrate underlying SS of the MPC in the rat.
Journal Article↗
Intracranial self-stimulation under a progressive-ratio schedule in rats: effects of strength of stimulation, d-amphetamine, 7-OH-DPAT and haloperidol.
Progressive-ratio (PR) schedules, which have been widely used to study the reinforcing efficacy of various reinforcers (in particular IV psychostimulants), have been very seldom applied to the study of positively reinforcing electrical brain stimulation (EBS). In the present study, rats were required to emit a progressively increasing number of lever-presses (3,4,6,7,9,11,14,16, etc.) for access to successive reinforcers (periods of VTA self-stimulation). Each period of self-stimulation consisted of ten trains of square pulses of EBS; each train was available under a continuous reinforcement schedule. The number of periods of EBS earned during a session was deemed the breaking point (BP). After acquisition and stabilization of self-stimulation, a study was carried out to verify that changes in the strength of the EBS (i.e. changes in the frequency, the intensity or the pulse duration, one parameter at a time) induced changes in the BP. The effects of IP pretreatments with d-amphetamine, the dopamine D3/D2 receptor agonist 7-OH-DPAT and haloperidol were then assessed. Decreases in the strength of EBS decreased the BP. However, increasing the strength above training values resulted in minimal increases in the BP. d-Amphetamine (0.25-1 mg/kg) dose-dependently increased the BP; additionally, when the reinforcer was withheld (i.e. in conditions of extinction, with the stimulator turned off) d-amphetamine was also found to augment the BP. This might indicate that d-amphetamine preferentially potentiated the motivational (non-rewarded presses) aspects of VTA self-stimulation under this type of PR schedule. 7-OH-DPAT had biphasic effects: at low doses (0.01 and 0.03 mg/kg), it tended to decrease the BP while higher doses (1 and 3 mg/kg) robustly increased the BP. Under conditions of extinction, 7-OH-DPAT (1 mg/kg) had a tendency to increase the BP, but this effect was not statistically significant and did not approach the magnitude of effects observed with d-amphetamine. Haloperidol (0.08-0.48 mg/kg IP) dose-dependently reduced the BP, suggestive of a decrease in the reinforcing efficacy of the EBS. These results show that rats can be trained to self-administer EBS of the VTA under a PR schedule of reinforcement and that this behaviour is sensitive to disruption or potentiation of dopaminergic neurotransmission.
Animals↗
The effect of microinjections of amphetamine into the neostriatum and the nucleus accumbens on self-stimulation behaviour.
The effect of micro-injections of dexamphetamine chloride into the neostriatum, the nucleus accumbens, the anterior hypothalamus, and the ventricular system on self-stimulation with electrodes in the ventral tegmentum was studied. Unilateral injections of 10 mug into the anterior hypothalamus produced no effect. Injections into the neostriatum tended to depress the self-stimulation rate, whereas injections into the nucleus accumbens increased the rate markedly. Bilateral injections (2 times 2.5 mug and 2 times 5 mug amph.) into the nucleus accumbens were more effective than unilateral injections and were as effective as systemic injections of 1 mg/kg amphetamine (i.p.). Bilateral injections into the neostriatum also increased the self-stimulation rate. Injections of 10 mug into the ventricular system resulted in a smaller increase which was not statistically significant. These results are discussed in relation to the involvement of the dopaminergic system in the maintenance of self-stimulation behaviour.
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Integration of free pulses in electrical self-stimulation of the rat brain.
Frequency thresholds for electrical self-stimulation of the medial forebrain bundle were estimated in rats while low frequencies of pulses were applied continuously. When continuous pulses were delivered to the same electrode that received the 0.5-s trains of response-initiated stimulation, thresholds decreased by the free-pulse frequency (Experiment 1), consistently across current (Experiment 2). Estimates of the reward added by concurrent, response-contingent stimulation of the opposite electrode of a bilateral pair predicted the drop in threshold caused by the noncontingent pulses applied to the opposite hemisphere (Experiment 3), again, robustly across test current (Experiment 4). Continuous pulses restricted to times between self-initiated trains lost their effect (Experiment 5). The perception of reward was invariant despite changes in the overall activity of the self-stimulation substrate.
Animals↗
Differential effects of pimozide on response-rate and choice accuracy in a self-stimulation paradigm in mice.
Intracranial self-stimulation (ICSS) from the dopamine (DA) A9 cell grouping was evaluated in mice following pimozide administration in both a one hole head dipping task and a two hole discrimination paradigm. While pimozide reliably decreased response rates, choice accuracy in the discrimination paradigm was unaffected by the drug treatment. The data were taken to suggest that neuroleptics influence response rate owing to motoric disturbances, without influencing the effectiveness of cues that previously had been associated with primary reinforcement.
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The effects of ventral tegmental administration of GABA(A), GABA(B), NMDA and AMPA receptor agonists on ventral pallidum self-stimulation.
The ventral pallidum (VP) is a basal forebrain structure that is interconnected with motor and limbic structures and may be considered as an interface between motivational and effector neural signals. Results from a considerable number of studies suggest that this structure is critically involved in reward-related behavior. The VP shares reciprocal connections with other reward-implicated regions, such as the ventral tegmental area (VTA). This anatomy predicts that drug-induced neuronal alterations in the VTA could profoundly alter the function of the VP. Here, using the curve-shift intracranial self-stimulation method, we studied the effects of muscimol (GABA(A) agonist), baclofen (GABA(B) agonist), NMDA and AMPA, microinjected bilaterally into the VTA on the rewarding efficacy of VP self-stimulation. Central injections of the highest dose of muscimol (0.128 microg) resulted in significant elevations in VP self-stimulation thresholds, indicating a reduction in the rewarding efficacy of the stimulation. Elevations in VP self-stimulation thresholds were also evident after intrategmental injections of higher doses of baclofen (0.12, 0.48 microg). By contrast, intrategmental activation of NMDA and AMPA receptors did not affect reward thresholds. These findings suggest that GABAergic and glutamatergic transmission in the VTA activate different circuits that may mediate different functions. Thus, the VTA--VP projection activated by GABA modulates VP stimulation reward, while the projection activated by glutamate may be involved in reward-unrelated effects, rather than in the processing of reward. The decreased rewarding efficacy of VP self-stimulation following intrategmental injections of muscimol and baclofen may be due to GABAergic modulation of ventral tegmental dopaminergic and nondopaminergic neurons projecting to the VP.
Animals↗
Similar potencies of CCK-8 and its analogue BOC(Nle28;Nle31)CCK27-33 on the self-stimulation behaviour both are antagonized by a newly synthesized cyclic CCK analogue.
Neurons with co-localized cholecystokinin (CCK) and dopamine (DA) are present predominantly in the ventral tegmental area (VTA) and project mainly to the caudal part of the medial nucleus accumbens. The activity of this dopaminergic system can be evaluated by means of the intracranial self-stimulation behaviour (ICSS) on male Wistar rats having chronic electrodes implanted into the medial forebrain bundle in the postero-lateral area of the hypothalamus. The direct injection of the CCK analogue BOC(Nle28;Nle31)CCK27-33 (BDNL-CCK7) into a lateral ventricle decreased the electrical self-stimulation of the medial forebrain bundle. Nevertheless, this decrease in self-stimulation was steeper (immediately after the injection vs a delay of +/- 5-10 min.) than the CCK8-induced ICSS depletion. The intracerebroventricular (ICV) injection of 150 pmol and 1000 pmol BC-197 (BOC-D.Asp-Tyr(SO3H)-Nle-D.Lys-Trp-Nle-Asp-Phe-NH2) was ineffective to modify the self-stimulation behaviour when administered alone while a 150 pmol BC-197 dosage was able to antagonize the decreasing effect of 150 pmol CCK-8 on ICSS. Nevertheless, a dosage 6 times as important, i.e. 1000 pmol BC-197, was needed to antagonize the depression induced by 150 pmol BDNL-CCK7 on ICSS behaviour. These results support the equipotence of BDNL-CCK7 to CCK-8 in decreasing the self-stimulation behaviour after their direct administration into the lateral ventricle. They further give evidence of the relevance of BC-197 in antagonizing the respective effects of both compounds on the ICSS.
Animals↗
Effects on hypothalamic self-stimulation of drugs influencing dopaminergic neurotransmission injected into nucleus accumbens and corpus striatum of rats.
The role of the nucleus accumbens septi (ACB) and corpus striatum (CPU) in self-stimulation were investigated by injecting directly or indirectly acting stimulant drugs or a dopamine-(DA)-receptor blocking agent into each site bilaterally. d-Amphetamine (68 nmol) facilitated hypothalamic self-stimulation when injected into either side. Apomorphine (40 nmol) depressed or facilitated responding, the direction and magnitude of this effect being contingent (C = 0.52) on the effect of systemic injection (0.3 mg/kg.i.p.), and correlated with the difference between the effects of d- and l-amphetamine (0.5 mg/kg i.p.) but not with injection site. Haloperidol (6.6 nmol) in either site depressed self-stimulation. Tyramine (730 nmol), an agent believed to cause noncontingent displacement of transmitter from catecholamine terminals, depressed self-stimulation when injection into CPU, but facilitated it when injected into ACB. The site-specific effects found with tyramine but not with apomorphine may have been due to release by tyramine of transmitters other than DA.
Amphetamine↗
Effects of the cannabinoid receptor agonist CP 55,940 and the cannabinoid receptor antagonist SR 141716 on intracranial self-stimulation in Lewis rats.
Lewis rats were trained to self-stimulate the medial forebrain bundle (MFB) using a rate-frequency paradigm. They were then tested for the effects of the cannabinoid receptor agonist CP 55,940, the selective cannabinoid receptor antagonist SR 141716 and the dopamine D1 receptor antagonist SCH 23390. CP 55,940 (0, 10, 25 and 50 microg/kg i.p.) had no effect on MFB self-stimulation behaviour as assessed by the M50, the stimulation frequency at which half-maximal response rates were obtained. With SR 141716, only a very high dose (20 mg/kg i.p.) caused a significant inhibition of the rewarding efficacy of the stimulation. This was seen as an increase in the M50. All other doses of SR 141716 (0, 1, 3, 10 mg/kg i.p.) were ineffective in modulating the M50. By comparison, a relatively low dose (0.06 mg/kg i.p.) of SCH 23390 caused a large increase in M50. These results indicate a relatively modest influence, if any at all, of exogenous or endogenous cannabinoids on reward-relevant neurotransmission.
Animals↗
Increasing spontaneous play by suppressing self-stimulation in autistic children.
Appropriate play with toys was studied in two autistic children with high occurrences of self-stimulatory behavior. Each child participated in the experimental sessions in an A-B-A design, where "A" refers to baseline sessions and "B" refers to self-stimulation suppression sessions. It was found that: (a) during the baseline sessions, the children exhibited low levels of play and high levels of self-stimulatory behavior; (b) the per cent of unreinforced, spontaneous, appropriate play increased when self-stimulatory behavior was suppressed; and (c) when the suppression of self-stimulation was discontinued, the per cent of self-stimulation and that of appropriate play approached their presuppression levels. These results seem particularly significant because they identify a set of conditions under which spontaneous appropriate behavior, uncommon in autistic children, occurs at an increased level.
Autistic Disorder↗
Intracranial self-stimulation after paradoxical sleep deprivation induced by the platform method in rats.
Lateral hypothalamic intracranial self-stimulation was studied before and after paradoxical sleep deprivation (PSD) induced by the platform method. Rats were assigned to two counterbalanced groups where the sequence order of experimental (small platform) and control (large platform) treatments was permuted. In contrast with previous findings significant changes in the response rates for intracranial self-stimulation were not observed after PSD. Ineffectiveness and nonspecific effects of the treatment are ruled out as the cause for our findings. An hypothesis is suggested that the effect of PSD upon intracranial self-stimulation could be dependent of the brain electrode location.
Animals↗