Effects of hippocampal damage on reward threshold and response rate during self-stimulation of the ventral tegmental area in the rat

The main purpose of this study was to explore the role of the hippocampus in motivated behavior. Rats with bilateral excitotoxic lesions of the hippocampus and controls were trained to lever press for electrical stimulation of the ventral tegmental area. Rate intensity functions were generated from an ascending and descending series of current intensities. Lesion-induced changes in sensitivity to reward were distinguished from enhancements in motor output by calculating reward thresholds and maximal response rates from the rate-intensity functions. Rats with hippocampal damage showed lower reward thresholds and higher maximal response rates than controls. These results provide further evidence of hippocampal modulation of the nucleus accumbens, suggesting that lesions of this structure enhance sensitivity to reward and increase motor output

At What Stage of Neural Processing Does Cocaine Act to Boost Pursuit of Rewards?

Dopamine-containing neurons have been implicated in reward and decision making. One element of the supporting evidence is that cocaine, like other drugs that increase dopaminergic neurotransmission, powerfully potentiates reward seeking. We analyze this phenomenon from a novel perspective, introducing a new conceptual framework and new methodology for determining the stage(s) of neural processing at which drugs, lesions and physiological manipulations act to influence reward-seeking behavior. Cocaine strongly boosts the proclivity of rats to work for rewarding electrical brain stimulation. We show that the conventional conceptual framework and methods do not distinguish between three conflicting accounts of how the drug produces this effect: increased sensitivity of brain reward circuitry, increased gain, or decreased subjective reward costs. Sensitivity determines the stimulation strength required to produce a reward of a given intensity (a measure analogous to the KM of an enzyme) whereas gain determines the maximum intensity attainable (a measure analogous to the vmax of an enzyme-catalyzed reaction). To distinguish sensitivity changes from the other determinants, we measured and modeled reward seeking as a function of both stimulation strength and opportunity cost. The principal effect of cocaine was a two-fourfold increase in willingness to pay for the electrical reward, an effect consistent with increased gain or decreased subjective cost. This finding challenges the long-standing view that cocaine increases the sensitivity of brain reward circuitry. We discuss the implications of the results and the analytic approach for theories of how dopaminergic neurons and other diffuse modulatory brain systems contribute to reward pursuit, and we explore the implications of the conceptual framework for the study of natural rewards, drug reward, and mood

Re-evaluation of the role of dopamine in intracranial self-stimulation using in vivo microdialysis

Rats were implanted with an electrode-microdialysis assembly in order to test the hypothesis that the reward signal elicited by medial forebrain bundle stimulation is relayed by the meso-accumbens dopamine cells. We first obtained the strength-duration function of selfstimulation, that is, a family of behaviorally equivalent stimuli (pulse intensity and pulse duration pairs yielding a constant self-stimulation rate). We then collected the self-stimulation-bound intra-accumbens dopamine for several pairs of intensity and duration, selected from within the strength-duration function. Our reasoning was that if the reward signal travels along the meso-accumbens dopaminergic neurons, the release of dopamine should not depend on the stimulus parameters because behaviorally equivalent stimuli should produce a constant output in all neural stages carrying the reward signal. The results showed that short duration/high intensity pulses induced considerably larger increases in dopamine levels than long duration/low intensity pulses, despite the fact that these stimuli maintained a constant self-stimulation rate. Among the interpretations envisaged, the most parsimonious one seems to be that the MFB rewarding signal is not relayed exclusively by mesoaccumbens dopaminergic cells and that the latter may play a permissive-facilitator role at some transmission stage of the reward signal

Alteration of cyclic nucleotide levels in brain following intracranial self-stimulation in the rat

In a first experiment, 14 rats were implanted with an electrode in the ventral tegmental area and trained to self-stimulate. On the experimental day only half of the rats were allowed to self-stimulate for one hour. All rats were then sacrificed by immersion in liquid nitrogen. Seven brain regions were dissected and assayed for the endogenous concentration of cyclic nucleotides. Self-stimulation induced significant changes in striatum and hippocampus. However, a subsequent experiment showed that the same pattern of changes in the striatum can be produced by motor activity. On the other hand, changes in the hippocampus were specific to the self-stimulation group suggesting that this structure is associated with the brain reward system