[Electrophysiological analysis of the effect of atropine on the self-stimulation reaction in cats].
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Kinetics of cell growth of human B-lymphocyte lines derived from Burkitt's lymphomas and lines derived from the Epstein-Barr virus transformation of normal adult lymphocytes were studied. Cells seeded at high densities (5 X 10(4)/ml) grew in an exponential manner; those seeded at low densities (5 X 10(3) to 1 X 10(4) began to grow exponentially only after a lag period of 3 to 4 days. Transfer of stationary low-density cell populations into filtered media from growing high-density cultures (conditioned media) stimulated cell growth, as determined both by increased cell numbers and [3H]thymidine incorporation. Enhanced cell growth occurred in conditioned media at all cell seeding concentrations that grew in normal media. Furthermore, cultures seeded at very low cell concentrations that do not grow in normal media proliferated in conditioned media. Media from a series of B-cell lines tested with one exception were autostimulatory. Reciprocal cell transfer experiments showed that media from B-cell lines cross-stimulated cells in other B-cell lines. Media from the non-B-cell lines tested were not autostimulatory and did not stimulate growth of the B-cell lines, and conversely these non-B-cell lines were not growth enhanced by the conditioned media. Absorption of growth-enhancing media with preincubated cell lines seeded at low density removed the enhancing capacity. These results demonstrate that B-cell lines from Burkitt's lymphomas and B-cells transformed in vitro by Epstein-Barr virus produce absorbable growth-enhancing factor(s) that may be essential to the development of perpetual growth in culture.
In self-stimulation behavior, the rate-frequency (R-F) function relates bar-pressing performance to the number of cathodal pulses of constant intensity, delivered in a train of fixed duration. The lateral position of the R-F function depends on the rewarding efficacy of the stimulation; a shift of the function toward larger pulse numbers after some experimental manipulation indicates a decrease in the efficacy of the stimulation. Because self-stimulation is often accompanied by stimulation-contingent motoric reactions, it is required to show that such reactions do not alter the estimates of rewarding efficacy of the stimulation. We describe an experiment in which the presence and severity of motoric reactions were controlled experimentally by simultaneous stimulation through a second electrode, located in a motoric brain region. Rats were implanted with one hypothalamic (LH) electrode (which elicited self-stimulation) and one reticular (RF) electrode (which elicited head and body movements). The rate-frequency function for each LH electrode was obtained under a single-pulse condition (LH electrode alone) and under a paired-pulse condition repeated three times, in which each LH pulse was accompanied by three different intensities of an RF pulse. Despite its severe effect on the slope and the asymptotic rate of R-F function, the interfering reaction failed to shift the R-F function to any significant degree. We concluded that these interfering reactions do not alter the estimates of neuronal density obtained through application of the curve-shift paradigm.
Electrical stimulation of the substantia nigra elicited complex patterns of response composed of somatomotor and circulatory changes. Increase in blood pressure associated with acceleration in heart rate was consistently produced by substantia nigra stimulation both in conscious and in anaesthetized cats. The respiration was either accelerated or arrested by the stimulation. Also self-stimulation of the substantia nigra elicited pressor responses. Electrical stimulation of the nucleus of the tractus solitarius paired with self-stimulation of the substantia nigra, produced regular changes in the lever-pressing rate for self-stimulation. It is suggested that the substantia nigra is probably involved in the neural mechanisms coupling the circulatory changes with the somatomotor responses.
OBJECTIVE: The aim of the present study was to examine whether self-care behaviour increases after a self-care stimulating intervention that proved to be successful in reducing care-seeking behaviour for minor illnesses of Turkish and Dutch inhabitants of a deprived area in the Netherlands, and to see whether there are cultural differences. METHOD: This longitudinal study was based on a "pre-test/post-test one group" design. Data were collected during three structured face-to-face interviews: before the intervention, and 6 months and 1 year after the intervention, in which GPs personally handed out booklets to their patients containing guidelines on the management of 12 minor illnesses. RESULTS: The number of self-reported self-care actions did not increase. In contrast to the Dutch, the Turkish participants reported a decrease in the number of self-care actions, their attitude towards self-care became more negative, and they perceived less control. CONCLUSION: Apparently, a reduction in formal health care utilisation is not engendered by an increase in self-care behaviour. In order to make sure that interventions like these will have the intended effect, more research is needed, particularly among non-western populations. PRACTICE IMPLICATIONS: In developing future healthcare-reducing interventions, one should be aware of possible unwanted side effects in non-western populations.
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The electrical self-stimulation paradigm has proven to be very useful in research aimed at delineating the neural substrates involved in reward-related learning. Of the procedures currently employed the curve-shift method is among the more useful since it distinguishes between treatment effects on reward and performance. This method involves generating and plotting rate-frequency functions and quantifying the effects of experimental manipulations on reward by measuring the degree of lateral shift in these functions. We have designed a computerized system that automatically generates and collects descending rate-frequency functions from self-stimulating rats. The 3 main units of this system consisted of a 6809 micro-controller, a programmable timer logic board and a constant current source. The micro-controller and programmable timer operated on custom written software that monitored lever pressing in the operant chambers and controlled stimulation parameters to generate and record rate-frequency functions. The present report describes this system and presents some typical data collected from rats self-stimulating on ventral tegmental electrodes before and after the administration of intra-accumbens vehicle (0.5 microliter distilled H2O), (+)-amphetamine (20.0 micrograms/0.5 microliter), quinpirole (10.0 micrograms/0.5 microliter) and systemic quinpirole (1.0 mg/kg), all dopamine agonists. Stimulation consisting of 300-ms trains of cathodal rectangular pulses (0.1 ms) was available in 50-s trials. The number of pulses per train was decreased logarithmically from a value that sustained maximal responding to one that would not sustain responding. Self-stimulation thresholds were obtained by fitting the Gompertz growth model to the data and calculating the point of maximal acceleration of the sigmoidal curve. It was found that the present system generated and collected rate-frequency functions similar to those that have been obtained manually in previous experiments. The data showed that the system was sensitive to both central and systemic pharmacological manipulations by producing lateral and vertical shifts of the rate-frequency functions, indications of reward and motor effects, respectively. It was concluded that the present design was useful in conducting entire self-stimulation sessions that required minimal monitoring by the experimenter.
Intracranial self-stimulation was assessed by the curve-shift method before and after D-amphetamine (1 mg/kg, i.p.) or vehicle injections given 8 times at 48-h intervals. Locomotor was assessed, in a separate test box, for the hour following the 35-min self-stimulation sessions. Amphetamine facilitated self-stimulation, shifting to the left the function relating response rate to stimulation frequency. The drug was most effective the first time it was given; the effects were weaker but unchanging across the remaining 7 days of repeated testing. When control animals that had been given vehicle for the eight initial days of testing were subsequently treated with amphetamine, it facilitated the behavior to the same extent as was seen the first time it was given in the experimental group. Amphetamine significantly increased locomotion in the period following the self-stimulation tests, and the degree of increase grew slightly but steadily with repeated testing; there was more rapid sensitization to this response in animals that were not subjected to self-stimulation testing prior to activity testing. These data do not fit well with earlier reports of sensitization to the reward-enhancing effects of amphetamine and reflect a potential dissociation between the locomotor-stimulating and reward-facilitating effects of amphetamine.
The effect of hypothalamic self-stimulation on colonic temperature and the effect of cold and warm environments on self-stimulation rate were assessed in 97 rats. In most of the rats, self-stimulation induced a rise in colonic temperature. However, in seven animals the reverse occurred. In the whole sample self-stimulation was significantly depressed by the warm environment. The cold environment facilitated self-stimulation at some placements and inhibited it at others. From the first six placements most facilitated by the cold environment five were also most inhibited by the warm environment. When allowed to self-stimulate in the cold environment high rate self-stimulators had a significantly lower colonic temperature than when they self-stimulated at 25 degrees C while low rate self-stimulators had the same or a higher colonic temperature. Body temperature changes induced by self-stimulation on the one hand, and the effects of the cold and warm environments on self-stimulation on the other appear to be independent one from another. The results suggest that among distinct types of hypothalamic rewarding loci a few might be specifically related to temperature regulation.
Aspects of the topography and behavioural function underlying the challenging behaviours of all people with learning disabilities and challenging behaviour (n = 70) in a defined geographical area were investigated. Results indicated that: (1) more severe challenging behaviours were shown by people with more severe disabilities; (2) a significant minority (44%) of people showed more than one form of challenging behaviour, this rising to 79% among people with more severe challenging behaviours; and (3) cross-sectional analyses revealed specific clusters of problematic, aggressive and self-injurious behaviours. Analysis of information derived from the Motivation Assessment Scale (MAS) indicated that (5) the most common functions of challenging behaviours appeared to be 'self-stimulation' (for self-injury, destructiveness and 'other' challenging behaviours) and securing the attention of carers (for aggressive behaviours). However, (6) parametric analyses failed to identify any consistent relationships between the form and function of an individual's challenging behaviour for aggressive, destructiveness and 'other' challenging behaviours, but (7) clients with self-injurious behaviour were significantly more likely to score highly on the 'self-stimulation' sub-scale than other sub-scales of the MAS. Finally, (8) significant consistency of behavioural functions across different forms of challenging behaviours shown by the same individual were found for the two combinations of aggressive-destructive behaviours and self-injury-'other' behaviours.
The interaction between morphine and lateral hypothalamic self-stimulation in rats was investigated in three experiments. In nonaddicted animals injections of moderate doses of morphine (8 mg/kg) resulted in a short-lasting increase in the self-stimulation threshold. Injections of low doses (2 mg/kg) did not alter the self-stimulation threshold significantly. In addicted animals self-stimulation thresholds were significantly lower 2 h compared to 22 h after injection of 200 mg/kg morphine hydrochloride (calculated as the salt). A 16 mg/kg injection of morphine in non-addicted rats suppressed self-stimulation. However, when the animals were administered noncontingent priming stimulation and were hand-shaped toward the lever whenever they left it, they continued to lever-press throughout the entire 90-min postinjection testing period. The animals that were neither primed nor shaped (and therefore remained unstimulated), however, showed a significantly better recovery when tested 90 min after the injection; i.e., their response rate was higher than that of the primed and shaped animals, which were engaged in bar-pressing throughout the entire testing procedure.
MK-801 (dizocilpine maleate), an antagonist of the NMDA receptor, was given alone or in combination with dopamine D1 and D2 receptor antagonists to rats self-stimulating in lateral hypothalamus to determine whether the dopamine neurons play a role in mediating the effects of MK-801. MK-801 given at a dose of 0.1 mg/kg i.p. to self-stimulators induced a prolonged facilitation of lever-pressing, but given to non-self-stimulators, the drug had no effects. Pretreatment of self-stimulators with the dopamine D1 receptor antagonist Schering 23390 (SCH 23390), 0.2 mg/kg given i.p. 15 min before MK-801, prevented the facilitation seen with MK-801, but did not suppress self-stimulation. SCH 23390 given alone suppressed self-stimulation. Pretreatment of self-stimulators with the dopamine D1/D2 receptor antagonist, haloperidol, 0.2 mg/kg given i.p. 15 min before MK-801, also prevented the facilitation of self-stimulation induced by MK-801 yet did not suppress self-stimulation. Haloperidol given alone suppressed self-stimulation. Pretreatment of self-stimulators with both SCH 23390 and haloperidol 15 min before MK-801 prevented the facilitation seen with MK-801 and suppressed self-stimulation. The combined treatment with SCH 23390 and haloperidol (without MK-801) suppressed self-stimulation, and the suppression lasted longer than the suppression seen when the two dopamine receptor antagonists were given as pretreatment, before MK-801. Pretreating self-stimulators with the combination of SCH 23390 and haloperidol 15 min before amphetamine (2 mg/kg) prevented the facilitatory response and suppressed responding for the brain reward. The suppression was of shorter duration than the suppression seen after the injection of SCH 23390 plus haloperidol. The treatment of self-stimulators with both MK-801 and amphetamine resulted in a greater and longer-lasting facilitation than the increase in responding produced by either drug alone. The similarity between the effects of MK-801 and those of amphetamine and between the effects of pretreatment with the dopamine receptor antagonists before MK-801 and before amphetamine suggests that dopaminergic activity played a significant role in the action underlying the effects of MK-801 on brain stimulation reward.
Chronic administration of amphetamine (AMPH) has been reported to produce tolerance to the drug's behavioral effects in some paradigms (self-stimulation, discriminative stimulus, self-administration) and an enhanced effect or reverse tolerance when other behaviors are monitored (locomotor activity, stereotypy). The present study investigated whether the two phenomena are, in fact, related to the particular behavior monitored or reflect the marked differences in the injection regimens (1X vs. 3X daily injections) used to produce the phenomena. The effects of chronic AMPH administered once or three times daily on AMPH facilitation of self-stimulation responding and on the locomotor stimulant and stereotypy-producing effects of the drug were assessed. Regardless of the injection regimen used, chronic AMPH resulted in an enhancement of the locomotor stimulant effects of the drug as well as a more rapid onset and greater intensity of the stereotypy produced. In the self-stimulation paradigm, only the 3X daily regimen significantly reduced the effectiveness of a challenge dose of AMPH (tolerance), although the 1X regimen produced effects that were qualitatively similar but quantitatively less. Perhaps behavioral tasks in which tolerance develops reflect the mood-altering properties of the drug in humans whereas a process similar to reverse tolerance may underlie the increased susceptibility to psychoses elicited by the drug with repeated use.
The refrcactory period of neurons mediating an electrically elicited behavior (self-stimulation) was estimated by varying the intrapair pulse separation in a stimulating train made up of pulse pairs and measuring the intensity of the elicited behavior. Two neuronal systems with different refractory periods were indicated. Single-unit recording in acute preparations stimulated through self-stimulation electrodes revealed primarily two classes of units. Each class gave refractory period estimates characteristic of one of the behaviorally indicated systems. The experiments illustrate a technique for establishing functional relations between single units in the brain and gross behavior.
It is known that lateral hypothalamic stimulation or self-stimulation can release dopamine in the nucleus accumbens (NAc). The present experiment illustrates that an aversively motivated behavior can also do this. Rats were prepared with microdialysis probes in the NAc and electrodes in the lateral hypothalamus (LH) or medial hypothalamus (MH). Automatic stimulation of the LH increased extracellular dopamine in the NAc 30% as reported earlier. The animals would perform both self-stimulation to turn the current on and stimulation-escape to turn it off, suggesting a combination of reward and aversion. Escape responding increased extracellular dopamine (DA) 100%, even though there was less total stimulation. Automatic stimulation of the MH did the opposite of the LH by decreasing accumbens dopamine (-20%), and the animals would only perform stimulation-escape, indicative of pure aversion. But again, extracellular DA in the NAc increased 100% during escape responding. Thus DA can be released during negative reinforcement when an animal's behavior is reinforced by escape from lateral or medial hypothalamic stimulation. This suggests that DA release was correlated with stimulation-escape behavior, rather than the aversiveness of automatic stimulation.
A monophasic pulse-pair stimulation technique was used behaviorally to infer neurophysiological interaction between 'reward' sites in the lateral hypothalamus (LH) and pain-implicated nucleus reticularis gigantocellularis (NGC). Rats lever-pressed for 3 s escapes from an otherwise continuous train of 0.1 ms NGC pulses delivered every 40 ms. When pulses to the LH were interdigitated with those to NGC, inter-response latencies were significantly longer. This occurred whether LH pulses were also interrupted by each lever-press (experiment 1) or not (experiment 2). Further, the same intensities of LH stimulation which inhibited escape supported high rates of lever-pressing for 3 s LH trains during inescapable NGC stimulation even though these LH trains were not of sufficient intensity to support 'rewarding' lever-pressing in the absence of NGC stimulation. This finding indicates that escape-inhibition in the first two experiments was not due to interfering motor effects of LH stimulation but most probably due to LH amelioration of NGC-induced aversion. Indeed, when aversion was ameliorated by morphine, lever-pressing for sub-reward-threshold LH stimulation during inescapable NGC stimulation decreased although classical self-stimulation did not. In the escape experiments, inhibition was greatest when each NGC pulse was preceded by an LH pulse at an interval of 0.1 or 10 ms. During inescapable NGC stimulation, rates of lever-pressing for LH trains were greatest when LH pulses preceded NGC pulses again at intervals of 0.1 or 10 ms. This congruence of the temporal bimodal profiles in the response functions of these two different behavioral experiments strongly suggests that the same integrative mechanism underlies both LH inhibition of NGC escape and lever-pressing for LH trains during inescapable stimulation of NGC. Since gastric loading did not alter lever-pressing for sub-reward-threshold LH trains during inescapable NGC stimulation but did inhibit classical self-stimulation, it was concluded that the inferred common integrative mechanism mediates a supraspinal gating of aversion which is independent of the LH self-stimulation reward process.