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.     

Plasticity of the medial prefrontal cortex: Facilitated acquisition of intracranial self-stimulation by pretraining stimulation

Prior electrical stimulation of the medial prefrontal cortex MFC facilitated the subsequent acquisition of intracranial self-stimulation (ICSS) from the same MFC electrode site. Stimulations that were spaced over a period of six days were more effective in producing this facilitation than the same number of stimulations delivered over a two day period. These data suggest that the rewarding effects of MFC stimulation may involve some process akin to the kindling phenomenon and as such may provide insights in the neuronal modifications thought to underlie learning and memory.     

Electrical self-stimulation of single and multiple loci: long term observations

Rats with chronic hypothalamic electrodes were allowed continuous access to self-stimulation, food and water in a 3 lever chamber. A prolonged burst of self-stimulation, with little food and water intake, was followed by bursts of activity on all 3 levers. A 12 hr light-dark cycle imposed a diurnal periodicity on all behaviors except in animals self-stimulating at the highest daily rates where self-stimulation was equal in dark and light. Under constant light conditions there was a 30 min daily shift in the peak periodicity of all behaviors. Increasing the current by 10 μA led to another continuous self-stimulation session for one day, with a subsequent decline and stabilization after three days. Reduction of the current to its original setting abolished self-stimulation for one day, but within 5 days rates returned to control values. Animals with electrodes in the septal, anterior and posterior hypothalamic areas allowed continuous access to self-stimulation on all 3 electrodes displayed similar behavior in that after a long initial self-stimulation session alternating on all 3 electrodes, periodic bursts of activity occurred on all three electrodes. The diurnal periodicity of self-stimulation seemed to be determined by the current intensity. The similarity of self-stimulation to normal drive mechanisms is discussed.     

Hypothalamic self-stimulation in the female rat: effects of oestrus and food deprivation.

Natural oestrus (147 cycles) had no overall effect in a longitudinal study of self-stimulation in a group of rats with hypothalamic electrodes (n = 20), though some individual animals showed significant increases in response rate at oestrus or at dioestrus. Animals were significantly more likely to show peak rates at prooestrus or oestrus if their electrodes were located in hypothalamic feeding areas; the effects in these rats were therefore probably indirect and non-sexual, caused by the decrease in food intake that accompanies oestrus. In ovariectomized rats, however, self-stimulation of feeding areas was usually unaffected by oestradiol injections, and increases in response rate reported after oestradiol injections in ovariectomized animals may therefore be a direct effect of the hormone; replicated study of the only animal showing unequivocal oestrogen-sensitive enhancement of self-stimulation showed that the effect was specific to oestrogenic (and not androgenic) steroids, and that the minimum effective dose was within the physiological range. These findings indicate both direct and indirect effects of oestrus on hypothalamic self-stimulation.     

Dependence of the anterior olfactory area self-stimulation upon the lateral hypothalamic area

The functional relation between the anterior olfactory area (AO) and the lateral hypothalamic area (LH) was examined in a self-stimulation situation. Bar-pressing responses for AO sitmulation were suppressed by unilateral injection of procaine, and enhanced by glutamate, into LH. Neither procaine nor glutamate injected into AO had any influence upon LH self-stimulation. It is unlikely that the procaine effect was due to motor disturbance because similar injection of procaine into LH did not disturb the performance of a one-way avoidance task. It appears that the rewarding effect of AO stimulation is dependent upon the excitation of the more caudal structures including LH.     

Development of brain stimulation reward in the medial prefrontal cortex: Facilitation by prior electrical stimulation of the sulcal prefrontal cortex

Electrical stimulation of the medial prefrontal cortex (MC) in rats delivered daily for seven days causes a marked improvement in the rate of acquisition of a self-stimulation response. In the present experiment, we looked at whether we could get the same facilitatory effect on self-stimulation of the MC by delivering pre-training stimulation to other points in the brain anatomically related to the MC. Electrical stimulation of the lateral hypothalamus was without effect. However, electrical stimulation of the sulcal prefrontal cortex (SC) either contralateral or ipsilateral to the MC electrode did facilitate acquisition of self-stimulation of the MC. Thus the SC and MC would appear to be part of the same substrate controlling the development of positive reinforcement in the MC.     

Alterations in short-term retention, conditioned avoidance response acquisition and motivation following aluminum induced neurofibrillary degeneration

Aluminum chloride induced neurofibrillary degeneration may provide a useful model for the study of a human dementia process. This possibility was assessed in cats trained to perform on a delayed-response task, a conditioned avoidance task, visual and temporal discrimination tasks and a motivational task involving rewarding intracranial electrical stimulation. After an initial asymptomatic period short term retention and acquisition of a conditioned avoidance response were selectively impaired. The associated ultrastructural abnormalities plausibly implicate the cytoplasmic streaming mechanism in the cellular substrate for some retention and acquisition phenomena.     

Response sensitization and depression following long-term amphetamine treatment in a self-stimulation paradigm

The effects of long-term amphetamine treatment were evaluated on responding supported by self-stimulation of the substantia nigra. Rats repeatedly treated with d-amphetamine, and tested with a low dose of the drug that ordinarily has no behavioral effect, showed higher response rates than animals repeatedly treated with saline and tested with the same dose of amphetamine. In contrast, a depression in responding was observed among animals that received long-term amphetamine administration and were tested with saline. The effects of long-term amphetamine treatment on self-stimulation could not be explained by the intrusion of drug-induced competitive behaviors such as locomotor activity and stereotypy. The results were attributed to changes in dopamine neurotransmission following prolonged exposure to amphetamine and were also discussed in terms of an animal model for amphetamine psychosis and postamphetamine depression in man.     

Effects of various catecholamine receptor antagonists, muscle relaxation and physical hindrance on shuttlebox self-stimulation

Certain drugs, particularly clozapine and clonidine, have been reported to increase selectively the latency to initiate brain stimulation (the ON latency) in a shuttlebox test of self-stimulation, suggesting a preferential attenuation of the "reward" component. The pharmacological selectivity of this reported effect was systematically evaluated. At doses that blocked bar-pressing self-stimulation, metoclopramide (3 mg/kg), prazosin (3 mg/kg) clonidine (0.1mg/kg), clozapine (3 mg/kg)and haloperidol (0.3 mg/kg), all elevated the ON latency to a greater extent than the OFF latency. Methocarbamol (200 mg/kg), and a muscle relaxant, also elevated the ON latency preferentially but the magnitude of this preferential effect was smaller than that produced by the other drugs. A hurdle in the center of the shuttlebox increased the ON and OFF latencies nonselectively. The shuttlebox procedure does not clearly discriminate among various substances that interfere with noradrenergic or dopaminergic neurotransmission, but the common profile produced by the these substances is distinguishable to some degree from simple motor disruption.