Synergistic effects of ethanol and cocaine on brain stimulation reward.

The effects of two widely abused drugs, ethanol and cocaine, were examined alone and in combination on intracranial reward processes. In agreement with previous research, higher doses of both cocaine and ethanol alone produced facilitation of behavior maintained by brain stimulation reward. Low intraperitoneal doses of ethanol and cocaine, which alone did not affect performance, were found to reduce stimulation reward threshold and modestly increase response rate. The enhancement of brain stimulation reward by the combination of ethanol and cocaine suggests that both drugs may produce their rewarding effects through common neuronal substrates and that they may potentiate the abuse of each other.     

Measuring threshold shifts for brain stimulation reward using the method of limits.

Thresholds determined from the frequency of pulses and the current for rewarding brain stimulation were obtained from rats with lateral hypothalamic electrodes. The threshold, defined as the frequency or current corresponding to one-half the maximum response rate, was interpolated from reward summation functions. Daily trials of both ascending and descending sequences of frequency and current yielded no significant difference between order of presentation. While there was more variability in the maximum response rates across the sessions, neither frequency- nor current-based threshold evaluations yielded significant rate effects. Our findings suggest that the threshold procedure is generally not influenced by the sequence of delivery of stimulus values and, thus, may be regarded as a reliable measure of the reinforcing properties of brain-stimulation reward.     

Neural substrate for brain stimulation reward in the rat: cathodal and anodal strength-duration properties.

The trade-off between current strength and duration of a stimulating pulse was studied for the rewarding and priming effects of brain stimulation reward (BSR). With cathodal pulses, strenght-duration functions for BSR had chronaxies of .8-3 msec. No differences were observed between the results for rewarding and priming effects. With anodal pulses. strength-duration curves were parallel to the cathodal curves at pulse durations of .1-5 msec, but at pulse durations greater than 5 msec the anodal curves showed a greater drop in required current intensity than did the cathodal curves. The parallel portion of the anodal curves was interpreted as due to anode-make excitation, and the drop at longer pulse durations was interpreted as due to anode-break excitation. Cathodal strength-duration functions for the motor effect elicited through the BSR electrodes had chronaxies of .15-.48 msec. Measurements of the latency of the muscle twitch confirmed that anode-make and anode-break excitation occurred, the latter becoming evident at pulse durations as brief as .3-.4 msec. The results provide quantitative characterization of cathodal and anodal strength-duration properties of the neural substrate for BSR and are discussed in terms of their value in guiding electrophysiological investigation of that substrate.     

Comparison of behaviors elicited by electrical brain stimulation in dorsal brain stem and hypothalamus of rats.

Four brain-stimulation phenomena elicited from both dorsal brain stem and hypothalamic sites were investigated with the following results: (a) intracranial self-stimulation rate-intensity functions for dorsal brain stem and hypothalamic sites yielded very high (over 1,000 responses/15 min.) to moderate (201-500 responses/15 min.) response rates; (b) d-amphetamine produced higher response rates than either l-amphetamine or saline at both dorsal brain stem and hypothalamic sites, indicating that noradrenergic dorsal brain stem fibers (or cell bodies) support intracranial self-stimulation; (c) dorsal brain stem and hypothalamic self-stimulation sites reliably produced escape behavior; (d) simultaneous stimulation of dorsal brain stem and hypothalamic sites at subthreshold intensities interacted to produce suprathreshold response rates.     

Self-stimulating rats combine subjective reward magnitude and subjective reward rate multiplicatively

For rats that bar pressed for intracranial electrical stimulation in a 2-lever matching paradigm with concurrent variable interval schedules of reward, the authors found that the time allocation ratio is based on a multiplicative combination of the ratio of subjective reward magnitudes and the ratio of the rates of reward. Multiplicative combining was observed in a range covering approximately 2 orders of magnitude in the ratio of the rates of reward from about 1:10 to 10:1) and an order of magnitude change in the size of rewards. After determining the relation between the pulse frequency of stimulation and subjective reward magnitude, the authors were able to predict from knowledge of the subjective magnitudes of the rewards and the obtained relative rates of reward the subject's time allocation ratio over a range in which it varied by more than 3 orders of magnitude.     

Bidirectional operant conditioning of heart rate in rats with sucrose reward

Sucrose was used to reinforce heart rate (HR) increases in one group of unrestrained rats and to reinforce decreases in another. A third group received noncontingent sucrose presentations, and a fourth was presented with an empty dipper. After 10 conditioning sessions HR, as measured by changes in tonic levels, was significantly greater in the Fast group than in the Noncontingent group, which in turn maintained significantly higher levels than the Slow group. There was no difference between the Noncontingent and No-sucrose groups. Behavioral observations indicated that the Fast animals increased the percentage of time spent in such high-HR categories as rearing and walking; however, there were no corresponding systematic decreases in the Slow animals. Moreover, the Fast and Slow groups differed significantly with regard to the HRs associated with five behavioral categories. The overall pattern of results suggests that some degree of cardiospecific effect may have been exerted by the operant contingencies.     

Social buffering in rats: prolactin attenuation of active interaction

Stress may result when the present environment is interpreted as threatening, and stress is known to increase the prolactin-secretory response. In the present study, rats (N=83) were exposed to a conditioned-fear paradigm (environment paired with footshock), and on testing day, rats were exposed to the experimental chamber without shock while alone (Alone n=16), with an object (Object n=17), with a euthanized conspecific (Euthanized n=16), or with a social partner (Social n=19). The control group (Control n=15) was exposed to the experimental chamber but was never shocked. The Control group had significantly lower levels of prolactin than the Alone, Object, and Euthanized groups; however, the Control group's levels of prolactin were not significantly different than that of the Social group, which was significantly lower than that for the Alone group. Social interaction decreased fear independent of the distraction provided by a stimulus in the chamber. Active touch appeared to be crucial for social buffering to occur.     

Frontal brain asymmetry and reward responsiveness: a source-localization study

The influence of approach and avoidance tendencies on affect, reasoning, and behavior has attracted substantial interest from researchers across various areas of psychology. Currently, frontal electroencephalographic (EEG) asymmetry in favor of left prefrontal regions is assumed to reflect the propensity to respond with approach-related tendencies. To test this hypothesis, we recorded resting EEG in 18 subjects, who separately performed a verbal memory task under three incentive conditions (neutral, reward, and punishment). Using a source-localization technique, we found that higher task-independent alpha2 (10.5-12 Hz) activity within left dorsolateral prefrontal and medial orbitofrontal regions was associated with stronger bias to respond to reward-related cues. Left prefrontal resting activity accounted for 54.8% of the variance in reward bias. These findings not only confirm that frontal EEG asymmetry modulates the propensity to engage in appetitively motivated behavior, but also provide anatomical details about the underlying brain systems.     

Runway performance of rats for brain-stimulation or food reward: effects of hunger and priming.

In a runway paradigm, pretrial electric stimulation of the brain (ESB), food deprivation, and to a lesser extent water deprivation increased the running speed of rats to an ESB reward. The trial-by-trail course of the change in running speed after the manipulation of food deprivation resembled the steplike performance effect seen when pretrial priming ESB is changed rather than the incremental learning effect seen when the response contingent ESB is changed. In a second experiment, pretrial ESB enhance rats' performance for an ESB reward, but act in opposing directions rats' performance for a food reward. Implications for Deutsch's model of self-stimulation are discussed.     

Vagus nerve stimulation: a new form of therapeutic brain stimulation

Although the vagus nerve has traditionally been considered to perform efferent functions, in reality it performs significant afferent functions as well, carrying information from the body, head, and neck to the brain. Preliminary studies examining this afferent activity led to the theory that vagus nerve stimulation (VNS) could successfully control seizure activity in persons who are refractory to antiepileptic medications. Unlike other forms of brain stimulation, VNS is unable to directly stimulate multiple discrete areas of the brain; however, through several pathways, it is able to relay sensory information to higher brain regions. An implantable VNS device known as the VNSTM NeuroCybernetic Prosthesis (NCP) System has been used in approximately 9,000 epilepsy patients in Europe and the United States since 1994. The implant has reduced seizure frequency by an average of 25% to 30%, with minimal side effects. Studies underway are also showing some degree of success in the management of treatment-refractory depression. The future efficacy of the implantable system in other disorders may depend on whether the implant can be more precisely focused to affect different brain regions. Research in this area is underway.     

Early stimulation and patterned responding in rats

This experiment was designed to determine the extent to which performance differences on learning tasks arising from infantile handling reflect learning or emotionality differences. Handled and nonhandled rats were trained and tested in a controlled operant situation where a response on every other trial yielded reinforcement. A key light was turned on for 10 sec during each trial and was off during the 10-sec intertrial interval. The reinforced (S+) trials alternated in a regular sequence with nonreinforced (S–) trials. The pattern of S+ and S– trials recycled continuously throughout the session of 160 trials. The handled rats emitted more responses during both S+ and S– trials than did the nonhandled rats. However, when they were compared on the percentage of emitted responses that were reinforced, there was no significant differences between the two groups. These results were interpreted to suggest that infantile handling does not directly facilitate associative learning in rats.This research was aided by a grant from the National Research Council of Canada, 67-0247. I thank Linda Easton and Beverly Clark for their help in collecting and analyzing the data.