Brain Stimulation Reward Thresholds Research Articles

Opioid-neuroleptic interaction in brainstem self-stimulation

Injection of morphine into the ventral tegmental area (but not dorsal to it) induced a dose-dependent decrease in the frequency threshold for midline metencephalic brain stimulation reward. Facilitating doses of ventral tegmental morphine also reversed, in 4 of 6 animals, the threshold-increasing effects of pimozide (0.35 mg/kg, i.p.). This reversal was itself reversed by naloxone (2 mg/kg, i.p.), suggesting a direct action of morphine at ventral tegmental opiate receptors. These data fit with electrophysiological evidence that ventral tegmental morphine stimulates or disinhibits dopamine impulse flow, which would result in increased synaptic dopamine concentrations and decreased synaptic pimozide effectiveness. In the remaining two animals, the combined neuroleptic-opiate treatment resulted in a complete cessation of responding that was not reversed by a 5-fold increase in stimulation frequency. This finding suggested a complete inactivation of the reward mechanism, which might be expected from the interaction of high doses of two drugs that are each known to be capable of producing depolarization inactivation of dopaminergic neurons. These data confirm that brainstem self-stimulation, like medial forebrain bundle self-stimulation, depends critically on the function of the mesocorticolimbic dopamine system.

The combined effects of morphine and d-amphetamine on the threshold for brain stimulation reward

The effect of morphine and d-amphetamine co-administration on the threshold for rewarding intracranial electrical stimulation was studied in rats with electrodes stereotaxically implanted in the medial forebrain bundle-lateral hypothalamic or ventral tegmental area of the brain. Thresholds were determined by means of a rate-independent psychophysical method. Individually, morphine and d-amphetamine both caused a dose-related lowering of the reward threshold. Low doses of morphine or d-amphetamine which were ineffective or minimally effective in lowering the reward threshold were then tested with various doses of either d-amphetamine or morphine, respectively. In both cases, the combined administration of morphine and d-amphetamine resulted in a lowering of the reward threshold that was greater than for the corresponding doses of morphine and d-amphetamine when given alone. Given that increased sensitivity for rewarding brain stimulation has been suggested to be an animal model of drug-induced euphoria, this effect is congruent with the reported increase in the degree of euphoria produced when amphetamine is used in conjunction with opiate drugs.

A multifunctional on-line brain stimulation system

A flexible on-line electrical brain stimulation system designed for brain stimulation reward (BSR) research is described. A Cromemco Z-2D microcomputer is interfaced with a constant-current stimulator and a standard operant chamber. The system programs, written substantially in BASIC, calculate BSR threshold by two rate-independent methods, measure rate of operant responding, and determine resistance of the brain. Other software programs are used for training rats on complex schedules of reinforcement, for system hardware calibration, and for sophisticated statistical data analyses.

Chlorpromazine and brain-stimulation reward: Potentiation of effects by naloxone

Chlorpromazine (0.25–2.0 mg/kg IP) raised the threshold for brain stimulation reward in a dose-dependent manner in rats. Naloxone (4.0 mg/kg IP) administered alone was without effect on this behavior. However, this dose of naloxone administered concurrently with chlorpromazine produced substantial potentiation of the threshold increases. These resultsstrongly suggest a catecholaminergic-enkephalinergic involvement in the regulation of central reward processes.

Drug-potentiated differential rearing effects on brain stimulation reward

Threshold and response rate for brain stimulation reward (BSR) were determined in rats reared for 60 days in an enriched or an impoverished environment. No differences in threshold or rate were found. Subsequent injections of amphetamine or scopolamine at 1-week intervals slightly decreased threshold and significantly increased response rate in enriched relative to impoverished rats. Results suggest that subtle manipulation of brain catecholamines and morphology by rearing can have a strong influence on BSR at its site of action in forebrain.