A new view of the effect of dopamine receptor antagonism on operant performance for rewarding brain stimulation in the rat

Abstract

Like indirect dopamine agonists, pimozide does not alter the sensitivity of brain reward circuity but changes reward-system gain, subjective effort costs, and/or the value of activities that compete with ICSS. The 3D method is more sensitive and informative than the 2D methods employed previously.

Psychophysical inference of frequency-following fidelity in the neural substrate for brain stimulation reward

“…Recent work employing 3D methodology argues that the contribution of the DA neurons is brought to bear at or beyond the output of the integrator and that these neurons do not contribute significantly to the directly stimulated stage of the circuitry [22,24,26]. That view is consistent with the mismatch between the characteristics of the directly stimulated reward substrate inferred from behavioral trade-off experiments and the properties of midbrain DA neurons observed in electrophysiological studies [47].…”

“…The traditionally employed 2D measurement strategies, wherein performance is measured as a function of one independent variable (either pulse frequency or price), have the ability to detect an effect of a manipulation on the circuitry underlying intracranial self-stimulation. However, these methods cannot determine at what stage of processing the effect has arisen and may be significantly less sensitive than the 3D method [23,26]. Changes in the output of the directly stimulated stage, the scaling of integrator output, the subjective effort entailed in harvesting a reward, and in the value of alternate activities can all produce identical displacements of 2D response-frequency curves [21,22].…”

“…The model and associated three-dimensional (3D) measurement strategy have been used in previous studies to differentiate between actions of experimental manipulations on early and late stages of reward processing [21][22][23][24][25][26][27]. In the early versions of the model, perfect frequency following was assumed.…”

“…Which among them are good candidates for the directly stimulated stage of the neural circuitry subserving BSR? Although DA fibers are unlikely to contribute substantially to the directly stimulated stage of the MFB substrate (see section 5.4.1), performance for rewarding electrical stimulation of the MFB is powerfully influenced by changes in DA neurotransmission [22,24,26,55,56]. Thus, MFB fiber populations that provide direct or indirect input to midbrain DA neurons are promising candidates.…”

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

“…Indeed, drug effects on maximal response rates (in hybrid procedures) or response latencies (in discretetrial procedures) are often evaluated precisely because of their value in detecting motor impairment (Carlezon and Chartoff, 2007;. However, it is less well appreciated that drug-induced increases in ICSS might also result from nonselective performance effects (Hernandez et al, 2010;Trujillo-Pisanty et al, 2013), and an even more nuanced principle is that drug effects on operant responding may be rate dependent. "Rate dependency" posits that drug effects on rates of operant responding may be independent of the reinforcing stimulus and may instead be determined by baseline rates of behavior before drug administration (Sanger and Blackman, 1976).…”