Pattern of rewarding stimulation affects the development of conditioned taste preferences

Research was undertaken to assess the importance of a response contingency on the development of conditioned taste preferences (CTPs). Water deprived rats implanted with lateral hypothalamic electrodes were given access to a lever which produced rewarding brain stimulation (response contingent rewarding stimulation) or had the stimulation administered at a rate determined by the experimenter (non-contingent rewarding stimulation) after drinking a novel tasting (coffee) solution. Consumption of the novel tasting solution was measured in a subsequent preference test. The results indicate that while response contingent stimulation produces reliable CTPs, non-contingent stimulation shows no evidence of inducing such preferences at any of the stimulation parameters employed. It was concluded that a reliable rate free measure of the rewarding aspects of brain stimulation could not be developed using non-contingent rewarding brain stimulation in conjunction with the CTP paradigm.     

Conditioned taste preferences in the rat induced by self-stimulation

Water-deprived rats with lateral hypothalamic electrodes were allowed to drink a novel tasting solution for 10 min, followed immediately by 15 min of intracranial self-stimulation. During a subsequent free-choice test with water, these rats exhibited a strong preference for the novel-tasting solution. Rats presented with either self-stimulation alone or the novel solution alone did not exhibit any such preference. The preference for the novel solution by the rats that experienced the pairing of this solution with self-stimulation was interpreted as a conditioned taste preference.     

Response involvement in brain stimulation reward

The hypothesis that responding contributes to the reward value of brain stimulation was tested in two novel experimental paradigms. In the first experiment rats lever-presssed for rewarding brain stimulation during 90 sec periods. After each period the lever automatically retracted and experimenter-administered stimulation (EAS) was presented at the same rate and current parameters as during the self-stimulation (SS). The rats could demonstrate a preference for SS (vs EAS) by pressing a reset lever on the opposite wall of the test chamber. This action terminated the EAS and reinstated the SS-lever for an additional 90 sec. Results showed that the rats preferred to respond for stimulation than to have that same stimulation administered by the experimenter. This was true even when a signal preceded each train of EAS or when subjects had a great deal of previous EAS experience. In the second experiment conditioned taste preferences were observed following novel taste/SS pairings but not following novel taste/EAS pairings. The data from these two experiments suggest that responding contributes to the rewarding value of brain stimulation.     

Disruption of the connections between the mediodorsal and sulcal prefrontal cortices alters the associability of rewarding medial cortical stimulation to place and taste stimuli in rats

This study involved 2 tests of conditioned reward with self-stimulation (SS) of the prefrontal cortex. In Experiment 1, rats were tested for a conditioned taste preference (CTP) induced by pairing a novel flavor with SS of the medial prefrontal cortex (MC). Normal rats displayed a CTP. Rats with bilateral cuts of the connections between the MC and sulcal prefrontal cortex (SC) did not show a CTP. In Experiment 2, similar cuts had no effect on the ability of SC SS to promote a CTP, showing that the cuts spare the ability to learn a CTP. In Experiment 3, rats were tested for a conditioned place preference by pairing MC SS with environmental cues. Lesioned rats, but not intact rats, had a CPP. Results suggest the presence of prepotent relations, dependent on intrinsic prefrontal connections, between the rewarding effects of prefrontal stimulation and distinct sensorimotor domains.     

Algebraic summation of the affective properties of a rewarding and an aversive stimulus in the rat

The presentation of a novel flavor followed by an injection of lithium chloride, produced conditioned taste aversions that were attenuated or blocked by rewarding brain stimulation (BSR) at low and high current intensities, respectively. Conversely, flavor/BSR pairings produced conditioned taste preferences that were attenuated in a dose-dependent manner by lithium chloride. These data support the contention of Young (20–23) for the algebraic summation of the positive and negative properties of affective stimuli. The implications of this work for the measurement of brain-stimulation reward and the aversive effects of drugs are also discussed.     

Determinants of the slow acquisition of medical and sulcal prefrontal cortex self-stimulation: an individual differences approach.

Stimulation-naive rats were tested for motor activity during noncontingent electrical stimulation of the medial prefrontal cortex (MPC) or sulcal prefrontal cortex (SPC). Defecation during stimulation was also measured. The rats were then tested using a conditioned taste aversion paradigm for aversion to a novel flavor (0.1% saccharin) paired with stimulation. Finally, the rats were trained to acquire self-stimulation over 26 days of training. Large individual differences were seen in motor activity, defecation, and conditioned taste aversion to initial stimulation and in the subsequent speed of self-stimulation acquisition. In the MPC-stimulated group, acquisition speed was positively correlated with motor activity to initial stimulation and negatively correlated with defecation to this stimulation. In the SPC-stimulated group, the same correlations were evident, but only when rats suffering seizures prior to self-stimulation acquisition were excluded from the analysis. Such preacquisition seizures, which were only found in the SPC-stimulated group, retarded self-stimulation acquisition. In most rats, MPC or SPC stimulation failed to condition a taste aversion to saccharin. These results suggest that the slow acquisition of MPC and SPC self-stimulation may be partly related to the motor suppressive, aversive, and convulsive properties of initial stimulation.     

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.     

Contingent and non-contingent actions of sucrose and saccharin reinforcers: effects on taste preference and memory

Preference curves were generated by comparing 14 concentrations each of sucrose and saccharin in a 20-minute test in which rats were presented with a choice of a sweet solution and water. The most preferred concentration and one concentration above and one below the most preferred for both substances were studied further. The sucrose and saccharin solutions were contingently paired with novel flavors in a conditioned taste preference (CTP) paradigm. All of the sweet solutions enhanced the animals' subsequent conditioned taste preferences for the flavors. The lack of difference between the effects of the solutions in this paradigm suggest that they had similar rewarding values and that CTP's are established mainly on the basis of taste cues. In another experiment, post-training ingestion of sucrose solutions, injection of glucose and, to a much lesser extent, ingestion of saccharin solutions retroactively and non- contingently improved retention of a previously formed, classically conditioned association. The results indicated that this effect was mainly due to the post- ingestional effects of the sucrose solutions, although taste factors also had a slight influence. This series of experiments parallels previous findings with self-stimulation as the reinforcer. The results support the hypothesis that reinforcers have a dual action on behavior: the elicitation of affective states that, when paired with environmental stimuli, can influence future behavior towards those stimuli; and a non-contingent retroactive enhancement of retention of previously formed associations.     

Conditioned facilitation of brain reward function after repeated cocaine administration

Cocaine lowers brain reward thresholds, reflecting increased brain reward function. The authors investigated whether, similar to acute cocaine administration, cocaine-predictive conditioned stimuli would lower intracranial self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days, a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5 additional days. Thresholds were measured immediately before and 10 min after each injection. The initial 5 saline injections had no effect on thresholds, whereas cocaine significantly lowered thresholds for 20 days. There was no tolerance or sensitization to this effect of cocaine over days. During the last 5 days when cocaine administration was substituted with saline, rats demonstrated a conditioned lowering of thresholds during the 2nd daily ICSS session. These data demonstrate that cocaine-predictive conditioned stimuli induce a conditioned facilitation of brain reward function.     

Microinjections of nanogram amounts of sulfated cholecystokinin octapeptide into the rat nucleus accumbens attenuates brain stimulation reward

Microinjections of nanogram amounts of sulfated cholecystokinin octapeptide (CCK-8S) into the nucleus accumbens were examined for effects on intracranial self-stimulation (ICSS) derived from the ventral tegmental area (VTA). The results showed that CCK-8S dose-dependently antagonized VTA intracranial self-stimulation (ICSS) without affecting maximum response rates. CCK-8S also increased the current threshold required for ICSS. These findings were interpreted to suggest that CCK-8S attenuates brain stimulation reward derived from the VTA.     

Intracranial self-stimulation in cats under local anesthesia of the cervical vago-sympathetic trunk

The rate of intracranial self-stimulation (ICSS) decreased to 45% of control (P < 0.001) under local anesthesia (procaine) of the cervical vago-sympathetic trunk. No significant change in ICSS was obtained after intramuscular injection of the same dose of procaine. Anesthesia of the cervical vago-sympathetic trunk did not affect lever-pressings for food     

Motion sickness in guinea pigs (Cavia porcellus) indexed by body rotation-induced conditioned taste aversions

The presence of motion sickness in albino guinea pigs (Cavia porcellus) was examined by using a conditioned taste aversion (CTA) as an index. Eighteen animals were divided into three groups. One group received four pairings of a novel 0.15% saccharin solution followed by 20 min of body rotation at 70 rpm (on a schedule of 15 sec on and 5 sec off). Another group received four pairings of the saccharin solution followed by exposure to sham rotation. The third group experienced the rotation procedure following access to water. The group receiving the rotation procedure contingent on presentation of the novel saccharin taste exhibited a conditioned aversion to this fluid (relative to the control groups) over days of acquisition (p less than 0.01), which subsequently dissipated when rotation was no longer contingent on the presentation of the saccharin solution (extinction). These data thus demonstrate the presence of motion sickness in guinea pigs when CTA is used as an index.     

An easily constructed biphasic constant-current stimulator for intracranial self-stimulation

This paper describes a biphasic, constant-current stimulator that is appropriate for intracranial self-stimulation (ICSS) studies. The stimulator is made from components that are readily available in electronic supply stores at low cost. A printed circuit board has also been designed for the stimulator which facilitates its production. The device has proven extremely reliable in various ICSS paradigms.     

Two self-shaping methods for intracranial self-stimulation in rats.

Shaping an animal for intracranial self-stimulation (ICSS) by manual reinforcement of successive approximations to the desired response can be tedious and time-consuming and may produce inappropriate behaviors. To test alternative shaping methods, rats were implanted with bipolar electrodes aimed at the medial forebrain bundle; one group was shaped manually, another group was allowed to acquire the bar-press response for food reward before implantation and then ICSS was substituted for food, and a third group was allowed to shape themselves spontaneously for ICSS through exploratory behavior. It was concluded that spontaneous shaping produces stable responders with less investment of time and expertise than do the other two methods.     

Response of medial telencephalic neurons to stimulation in reinforcing sites in the medial forebrain bundle and ventral tegmental area.

Responses of 361 single units recorded extracellularly in various medial telencephalic loci (?2.5 mm from midline) to stimulation in behaviorally-verified, intracranial self-stimulation (ICSS) sites were studied in rats lightly anesthetized with halothane. Trains of 100 Hz stimulation in ICSS sites at behaviorally effective intensities produced widespread effects on telencephalic neurons; 78% showed a short-term response (duration <1.5 sec), a long-term response (duration several sec), or both. Most areas had no single predominant type of response and showed a mixture of ON and OFF short-term responses. Exceptional regions were the superficial layers of cortex, predominantly ON responses, and the lateral septal region, predominantly OFF responses. The responses in most regions were similar to barpressing ICSS in that they directly depended on pulse frequency, i.e., 100 Hz stimulation produced a stronger response than 50 or 25 Hz. The septal region was high in frequency dependent response whereas the globus pallidus and olfactory nuclei were low. Short-term OFF responses were more often frequency dependent than ON responses, particularly those associated with short-latency (?20 msec) spike discharges. Stimulation in two ICSS sites tested on the same neuron produced more mutual OFF responses than mutual ON responses. The results indicate that ICSS has pervasive influences in the telencephalon. Of these influences, the inhibitory types appear to be most consistently related to ICSS behavior.     

Evaluation of motivational effects induced by intracranial self-stimulation behavior

In the runway model of intracranial self-stimulation (ICSS) experimentation, the experimental animal is timed in running a fixed distance to depress a lever that releases electrical stimulation to an electrode implanted along its medial forebrain bundle. This ICSS has both a reward and a motivational component. Using the runway method and priming stimulation, we designed an experimental method for directly measuring motivation. An assessment of pharmacological agents that are known to influence motivational states was also undertaken. Using the experimental methods that we created, we observed prominent changes in running speed when animals were exposed to methamphetamine and nicotine. According to these data, the runway method employing intracranial self-stimulation behavior may be useful for the evaluation of substances that act on motivation. We review the underlying neuropharmacological and anatomical functions associated with our experimental methods. We hope that this technique will be used to scientifically evaluate the impact of drugs and/or therapeutic interventions on human motivation.     

An analysis of the behavior elicited by stimulation of the dorsal pons in rat

Dorsal pontine intracranial self-stimulation (ICSS) sites were electrically stimulated in rats. Only stimulation-induced oral behavior and not locomotor behavior was observed. The predominant elicited behavior was a fragmentary type of forepaw grooming. In some cases the stimulation-induced forepaw grooming was changed to drinking by the forced presentation of a drinking spout in the perioral region. Neither the dorsal pontine stimulation-induced oral behavior nor the ICSS was disrupted by six-hydroxydopamine lesions of ascending noradrenergic projections from locus coeruleus to widespread forebrain areas. It is suggested that the mesencephalic nucleus of the trigeminal nerve, with its connections to the motor trigeminal nucleus, may mediate dorsal pontine stimulation-induced behavior and ICSS.     

Housing conditions alter the acquisition of brain self-stimulation and locomotor activity in adult rats

Rats were implanted with stimulating electrodes in the medial forebrain bundle-lateral hypothalamus (MFB-LH). After recovery from surgery, they were assigned to one of two groups equalized for body weight. One group was housed four animals to a cage and animals in the other group were housed individually. After four weeks in these housing conditions, animals were tested during the fifth week for locomotor activity in five daily 15-min sessions, and their reactivity to handling was also measured. During the sixth and seventh weeks, animals were allowed to self-train for brain stimulation (ICSS) during daily 15-min sessions. Animals housed in groups had higher levels of locomotor activity and were less reactive to handling than were animals housed individually. When tested for the acquisition of ICSS, animals housed as a group made more responses than did animals housed individually. These results indicate that, within the time frame of a few weeks, the housing conditions of adult animals caused differences in both unconditioned behavior, such as locomotor activity, and in the acquisition of a highly reinforcing brain self-stimulation task.     

Measurement of intracranial self-stimulation thresholds using the post-reinforcement pause

A method for measuring the current threshold for intracranial self-stimulation (ICSS) using the post-reinforcement pause (PRP) is described. Rats trained to lever press on a fixed ratio schedule for ICSS in prefrontal cortex, medial forebrain bundle, ventral tegmental area or periaqueductal gray received stimuli of opposite polarity in an alternating fashion. Stimuli of one polarity were sufficient to maintain ICSS responding by themselves (maintaining stimuli). Stimuli of the other polarity were systematically varied in 5-10 microA steps (experimental stimuli). PRPs following both maintaining (Pm) and experimental (Pe) stimuli were measured, and the ratio Pm/Pe was calculated. The PRP threshold was defined as the lowest experimental stimulus current producing PRP ratios significantly less than the ratios produced by all lower current steps. After the PRP threshold for one polarity was determined in 5 daily sessions, the experimental and maintaining stimuli were reversed, and the PRP threshold was measured for the alternate polarity. Rates of ICSS on a continuous reinforcement schedule were subsequently measured at currents around the PRP threshold. Rates increased sharply at PRP threshold, suggesting a correlation between PRP threshold and reinforcement threshold. Similar results were obtained from all four ICSS sites indicating the broad applicability of the PRP threshold method.     

Effects of HR-592, a new derivative of indole, on conditioned behavior

Effects of HR-592, a new derivative of indole, on conditioned avoidance and intracranial self-stimulation behavior were investigated in rats using a shuttle box and a Skinner box, respectively. The oral administration of HR-592 at doses of 3-10 mg/kg caused a dose-dependent suppression of the conditioned avoidance response. Even the escape response was slightly suppressed in the group administered 10 mg/kg of HR-592. The self-stimulation behavior was suppressed dose-dependently from 1 to 8 h after the administration of 6-10 mg/kg of HR-592. These results indicate that the action of HR-592 on conditioned avoidance response and intracranial self-stimulation behavior is similar to the action of neuroleptics.