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A behavioral measure of homosynaptic and heterosynaptic temporal summation in the self-stimulation system of rats.

Bilateral stimulation of the medial forebrain bundle with pulses of varying interpulse intervals elicited a pattern of self-stimulation behavior in the rat indicative of temporal synaptic summation: the shorter the interval the greater the response. In contrast, the effectiveness of unilateral stimulation at very short intervals was limited by neuronal refractory periods. The results support the notion that there is convergence of the medial forebrain bundle self-stimulation system from the two sides of the brain and suggest ways of studying the degree of convergence. They also suggest a technique for behaviorally comparing heterosynaptic and homosynaptic mechanisms of summation.

Animals↗

Prefrontal cortex lesions attenuate substantia nigra self-stimulation: a reward summation analysis.

A curve-shift paradigm was used to assess the effects of lesions of the prefrontal cortex on self-stimulation from electrode sites in the substantia nigra. Combined lesions of the medial and sulcal cortical regions severely attenuated substantia nigra self-stimulation. These results are discussed in the context of the frontal cortex and the substantia nigra as belonging to a reinforcement system that is largely independent of the medial forebrain bundle system.

Animals↗

[Conjugation of the neuronal impulse activity in the rabbit neocortex during self stimulation of the lateral hypothalamus].

Correlation of impulse activity of visual and sensorimotor neurons of both hemispheres in 10-s interval after self-stimulation of the right and left lateral hypothalamus was studied by plotting cross- and autocorrelation histograms. The number of cell pairs, in which sensorimotor neurons discharged after visual ones, increased after self-stimulation (from 24 +/- 6 to 44 +/- 7%). Frequencies of the alpha- and theta-range in crosscorrelograms increased; the alpha frequency increased mainly in the right hemisphere, while the theta frequency increased in the left hemisphere. The interhemispheric asymmetry in the interaction between cortical neurons was not associated with the side of hypothalamic stimulation.

Animals↗

Self-stimulation alters human sensory brain responses.

Human electrocortical potentials evoked by self-administered auditory and visual stimuli manifest much smaller amplitude and faster poststimulus timing than do average brain responses evoked by identical machine-delivered stimuli. Auditory evoked potentials show this "self-stimulation effect" to a greater degree than do visual responses. For visual evoked potentials, the effect appears greater at the vertex association area than over the occipital cortex. Individual differences in the magnitude of the "self-stimutlation effect" relate to level of intelligence.

Acoustic Stimulation↗

[Biochemical mechanism of reinforcement: findings in the studies of self-stimulation].

Recent developments in the study of brain self-stimulation were reviewed with particular emphasis on the biochemical mechanism underlying the phenomenon. Several lines of evidence suggest that dopaminergic transmission in the mesolimbic system is critical for the reinforcement effect to occur. An important event is the activation of D2 dopamine receptors in the nucleus accumbens and its vicinity, but D2 receptors cannot respond to dopamine unless D1 receptors are activated first. It is necessary for these receptors to work together to initiate intracellular chemical reactions to alter the excitability of the accumbens neurons. Recent experiments suggest that the reinforcing effect of medial-forebrain-bundle stimulation depends on the activation of intracellular protein kinase in the nucleus accumbens. As in the sensitization in Aplysia and long-term potentiation in the hippocampus, protein kinases play critical role in the reinforcement of operant behaviour.

Brain↗

Fitting intracranial self-stimulation data with growth models.

Until now, the problem of fitting self-stimulation rate-frequency functions has been dealt with by using linear models applied to the linear portion of the empirical curve. In this article, an alternative procedure is presented, together with three sigmoid growth models that seem to accurately fit rate-frequency data. From any of these models, it is possible to compute the two indices of stimulation efficacy in use in the parametric study of brain stimulation reward (M50 and theta 0), in addition to the inflection point of the curve, which can be used as an alternative to M50. Important relations allowing initial estimation of each parameter are provided, allowing use of computer programs derived from the Gauss-Newton algorithm for nonlinear regression. The considerations relevant to the choice of a nonlinear model are discussed in terms of each efficacy index.

Algorithms↗

Dorsal noradrenergic bundle lesions fail to disrupt self-stimulation from the region of locus coeruleus.

Intracranial self-stimulation (ICSS) from the region of the locus coeruleus (LC) was not attenuated by ipsilateral dorsal noradrenergic bundle (DNB) lesions. Bilateral DNB lesions also failed to affect LC ICSS, whereas the same lesions, in the same animals, resulted in a marked enhancement of lateral hypothalamic (LHA) ICSS responding. Behavioral, neuroanatomical and fluorescent histochemical data confirmed destruction of the DNB, thus suggesting that the dorsal noradrenergic system is not necessary for ICSS from the region of the LC.

Animals↗

6-OHDA lesions of the ventral tegmental area block morphine-induced but not amphetamine-induced facilitation of self-stimulation.

The biphasic effect of morphine on intracranial self-stimulation (ICSS) (suppression followed by facilitation) was examined in rats following injections of 6-OHDA or vehicle into the ventral tegmental area (VTA). During 7 days of chronic administration of morphine, sham-lesioned animals gradually developed tolerance to the rate-reducing effects of the drug and a concurrent sensitization to its rate-enhancing effects (measured 1 and 3 h post-injection, respectively). VTA lesioned rats showed neither tolerance to the rate suppression nor any facilitation of ICSS throughout testing. Amphetamine's facilitation of ICSS remained intact in all subjects. The lesion was restricted to the VTA cell bodies but produced a significant depletion of dopamine (DA) in both the nucleus accumbens and in the striatum. Morphine facilitation of ICSS is suggested to be dependent on an indirect opiate receptor-VTA DA cell interaction. It is also proposed that amphetamine facilitation of ICSS is a 'mass action' effect involving the full DA terminal area of the forebrain rather than a subregion of that area.

Animals↗

Dopamine receptor sub-types involvement in nucleus accumbens and ventral tegmentum but not in medial prefrontal cortex: on self-stimulation of lateral hypothalamus and ventral mesencephalon.

The involvement of different sub-types of dopamine receptors in the electrical self-stimulation behaviour was investigated using DA receptor subtype specific agonists viz R(+) SKF 38393 and LY 171555 (quinipirole). Rats were chronically implanted with bipolar electrodes in lateral hypothalamus-medial forebrain bundles (LH-MFB) and ventral tegmental area-substantia nigra (VTA-SN) or guide cannula in nucleus accumbens (nACB) or medial prefrontal cortex (mPFRCx) or cannula-cum-electrode in VTA-SN. Combining these, it was possible to inject a given receptor ligand in either nACB or mPFRCx or VTA-SN and assess the changes in intracranial self-stimulation (ICSS) of LH-MFB or VTA-SN. The experimental subjects were trained to press a pedal to obtain 0.25 s trains of cathodal rectangular pulses of 0.1 ms pulse duration (for LH-MFB electrode) or 0.3 ms pulse duration (for VTA-SN electrode). The rate-frequency curve for each subject and each placement were obtained in order to determine M50 (50% of maximum asymptotic response rate). Microinjection of SKF 38393 (a D1 agonist) or LY 171555 (a D2 agonist) into nACB caused facilitatory and suppressive effects on the ICSS of VTA-SN and LH-MFB respectively. On the contrary, intra VTA-SN injection of 10 micrograms/0.5 microliter of SKF 38393 or of LY 171555, reduced its ICSS to half as compared to vehicle injections. Under the effect of these injections, there was no change in the ICSS of LH-MFB. The combined administration of SKF 38393 (5 micrograms) and LY 171555 (10 micrograms) into nACB produced suppression of ICSS of VTA-SN to greater extent than the LY 171555 (10 micrograms/0.5 microliter). This indicates that coactivation of D1 and D2 leads to suppression of ICSS of VTA-SN. The activation of D1 receptors in nACB facilitates the ICSS of both VTA-SN and LH-MFB by increasing the reinforcement and/locomotor activity, while the activation of D2 receptors in it has opposite effect. The coactivation of D1 and D2 receptors in VTA-SN leads to the suppression of ICSS of both VTA-SN and LH-MFB. Similar injections of these receptor ligands into mPFRCx did not alter the ICSS of either LH-MFB or VTA-SN. The pre- or post-synaptic DA receptors of mPFRCx do not appear to influence the ICSS of either VTA-SN or LH-MFB in any significant manner.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Neuropharmacological evidence for the role of dopamine in ventral pallidum self-stimulation.

The present study examines the role of dopaminergic neurotransmission in modulating the reinforcing effect of ventral pallidum (VP) intracranial self-stimulation (ICSS). Fifty four adult rats were implanted with a monopolar moveable stimulating electrode in the VP. Rate-frequency functions were determined by logarithmically decreasing the number of pulses in a stimulation train from a value that sustained maximal responding to one that did not sustain responding. After the ICSS thresholds stabilized, the animals received treatments with several doses of cocaine and of various selective drugs acting at the level of DA receptor subtypes. Their effects on threshold and asymptotic rate were analyzed. Cocaine produced a significant decrease in ICSS threshold but had no significant effect on the asymptotic rate. A significant decrease in ICSS threshold was also seen with the D3 agonist 7-OH-DPAT. This was associated with a decrease rather than an increase in performance. D1 and D2 DA receptor blockers (haloperidol, SCH-23390, raclopride and sulpiride) produced a dose dependent increase in ICSS threshold and a decrease in the maximal rate. The results suggest that DA plays a modulatory role in VP intracranial self-stimulation, and that D1, D2 and D3 receptors are involved in the mediation of this effect, although to different extents.

Animals↗

Behavioral correlates of self-stimulation, flight and ambivalence.

Behavioral phenomena consisting of approach (self-stimulation, SS), flight and ambivalence (approach-flight) elicited by intracranial stimulation (ICS) along the neuraxis from the forebrain to the hindbrain were filmed and analyzed. The main findings were: (1) approach, flight and ambivalence could be obtained from all levels of the brain; (2) no single fixed behavioral pattern was common to approach or ambivalence; (3) there were instead different patterns which varied according to the area but some of the individual features of these patterns were at times common to several brain areas; (4) exploration with sniffing was found to be the most frequent behavior accompanying both approach and ambivalence. For SS, exploration was organized in the following topographical manner: nonsystematically at the level of the dorsal pons, diffused at the raphé, scattered at the level of the ventromedial mesencephalon (VMT), and focalized at the level of the lateral hypothalamus; (5) the highest intensities of SS, flight and ambivalence were found in the more caudal areas, namely the VMT for approach, the posterior mesencephalic reticular formation for ambivalence and the ventral region of the reticularis pontis caudalis (RPC) for flight; (6) in approach behavior for SS, when the point of stimulation was changed from the medio-frontal cortex to the posterior hypothalamus and VMT, an orderly change from depression to excitation of locomotor activity appeared. However, in the case of the locus coeruleus (LC) and adjacent dorsal tegmentum, SS by bursts was correlated with either intense motor activity or transitory periods of adynamia followed eventually by progressive ambivalence after bursts of SS; (7) approach and ambivalence elicited from areas known or believed to be involved in sleep regulation (midbrain raphé, LC and proximal dorsal pontine areas) were accompanied by what at first appeared as disruptive behaviors; but other complex behaviors were noted which suggest that during alertness, these areas may be involved in behaviors that are phylogenetically important for the development of motor and cognitive functions and most likely also in the behavioral manifestations of major psychiatric illnesses.

Animals↗

Involvement of the trigeminal motor system in brain stem self-stimulation and stimulation-induced behavior.

Anatomical and behavioral correlates of intracranial self-stimulation (ICSS) at sites in the pons suggest the involvement of the trigeminal motor system in brain stimulation reward. 90% of the electrodes terminating in or dorsal to the trigeminal motor nucleus supported ICSS. Stimulation through these ICSS electrodes was usually accompanied by a display of repetitive jaw movement in the period following brain stimulation. There appeared to be a close relation between post-stimulation jaw movement and ICSS. In the motor nucleus there was a positive linear relationship between current intensity and duration of jaw movement. Optimal current intensities for ICSS induced long periods of jaw movement. Extensive lesions of the dorsal pons which included the locus ceruleus had no effect on ICSS in the trigeminal motor system. Therefore it seems unlikely that ICSS in the trigeminal system is mediated by noradrenergic neurons located in the dorsal pontine area. These data suggest that a centripetal analysis of ICSS sites along pathways afferent to the trigeminal motor system may lead to a more complete description of the anatomical correlates of brain stimulation reward. The functional implications of a trigeminal reinforcement mechanism are discussed.

Animals↗

Linked spike activity of rabbit neocortex neurons during self-stimulation of the lateral hypothalamus.

Cross-correlation and autocorrelation histograms were constructed to study the linkage between the spike activity of neurons in the visual and sensorimotor areas of both cerebral hemispheres in rabbits over periods of 10 sec after self-stimulation of the right and left lateral hypothalamus. Self-stimulation was followed by an increase in the number of pairs of cells in which neurons in the sensorimotor area fired after cells in the visual cortex (from 24 +/- 6% to 44 +/- 6%). Analysis of the spectrum of linked discharges revealed increases in the alpha and theta frequency ranges: the main increases in the right hemisphere were in the alpha range, while the main increases in the left hemisphere were in the theta range. Interhemisphere asymmetry in the interaction of cortical neurons was not associated with the side of the hypothalamus subjected to stimulation.

Animals↗

[Self-stimulation of phylogenetically new and ancient hypothalamic structures when reinforcement schedules are changed].

The following two types of reaction are exhibited by self-stimulating rats following a transition from the regimen of preference (free) to that of fixed series of stimuli: I. increased frequency of pressings with simultaneous shortening of their duration, approaching the duration of fixed series; II. reduced frequency of pressings with their longer duration. Of the two studied hypothalamic areas, the former type of reaction is exhibited predominantly in the self-stimulation points located in the lateral hypothalamic area, while the latter type - in the lateral preoptic area. Different strategy of the animals' behaviour observed during the change of reinforcement routines is discussed with regard to different levels of integration of emotionally-positive mechanisms of brain structures of phylogenetically different age.

Animals↗

Real time measurement of stimulated dopamine release in the conscious rat using fast cyclic voltammetry: dopamine release is not observed during intracranial self stimulation.

Fast cyclic voltammetry (FCV) was used to measure real time release of electrically stimulated endogenous dopamine in the nucleus accumbens (NAc) of conscious freely moving rats for up to 17 days. The method of electrode construction, implantation, electrical stimulation and recording of changes of extracellular dopamine concentration in the conscious rat are described. Rats trained on a continuous reinforcement schedule to perform intracranial self stimulation (ICSS) were implanted with electrodes for FCV. During ICSS, no faradaic signal was observed at an electrode implanted in the NAc. Decreasing the intensity of the stimulating current abolished ICSS, increasing the stimulating current disrupted ICSS. Operator delivered electrical stimulations using currents greater than those needed for ICSS yielded dopamine signals. It is concluded that during ICSS, sufficient dopamine does not reach the extracellular fluid space to yield a faradaic signal detectable by FCV.

Animals↗

Task-specific effects of nicotine in rats. Intracranial self-stimulation and locomotor activity.

The acute effects of nicotine (0.03-1.0 mg/kg) were studied in a locomotor activity procedure and in a series of intracranial self-stimulation (ICSS) paradigms. Nicotine produced a dose-dependent decrease in locomotor activity. When animals were trained to lever-press for intracranial self-stimulation on a continuous reinforcement schedule (CRF), the drug was ineffective except at the 1.0 mg/kg dose, which produced a moderate decrease in the rate of responding. However, when animals were tested in a fixed-ratio:15 (FR:15) paradigm, nicotine produced a steep, biphasic dose-response curve. At the 0.1 mg/kg dose, the response rates were increased to approx. 60% above baseline, while at the 1.0 mg/kg dose, response rates were decreased to approx. 90% below baseline values. The effects of nicotine were also studied in an auto-titration procedure which measured the rewarding value of the stimulus. There was a decrease in performance at larger doses similar to that observed in the continuous reinforcement procedure, but there were no significant changes in the threshold for reinforcement. Nicotine did not produce any change in the detection threshold for stimulation of the brain. In acute studies, therefore, nicotine produced both stimulation and disruption of behavior, effects that were brought to light by the fixed-ratio schedule of reinforcement, and this may relate to the rewarding effects of nicotine.

Animals↗

Effects of using object self-stimulation as a reinforcer on the prevocational work rates of an autistic child.

The purpose of this study was to examine the effects of object self-stimulation on the task-interrupting self-stimulatory behavior and prevocational work responses of a 13-year-old autistic boy. Using a multiple-baseline design across three different prevocational tasks, a systematic manipulation of object self-stimulation was associated with increases in correct rates and decreases in task-interrupting self-stimulatory behaviors. An analysis of these data indicates that self-stimulatory behavior may be shaped to facilitate performance proficiencies. Social validation information suggests that favorable generalized responding had occurred. On the basis of findings from this study, future research needs are discussed.

Adolescent↗