The role of dopamine in intracranial self-stimulation of the ventral tegmental area

Abstract

The role of dopaminergic (DA) neurons in brain stimulation reward produced by electrical stimulation of the ventral tegmental area (VTA) was investigated in the rat. In the first experiment, extensive 6- hydroxydopamine lesions of the ascending fibers of the mesotelencephalic DA projections resulted in significant changes in intracranial self-stimulation (ICS) rate-current intensity functions when the lesion was ipsilateral to the stimulating electrode. Similar contralateral lesions had no effect on these functions, thus ruling out lesion-induced performance deficits as being responsible for the decreases in ICS rates across the wide range of current intensities that occurred after the ipsilateral lesions. In the second experiment, ICS obtained from electrodes in the VTA resulted in significant increases in the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, nucleus accumbens, and olfactory tubercle ipsilateral to the stimulating electrode. The ratios of DOPAC and HVA to DA, considered to be indices of DA utilization, were also increased in these brain regions ipsilateral to the electrode. No changes were observed in the contralateral striatum, nucleus accumbens, and olfactory tubercle. Similar increases were observed in stimulated “yoked” animals that received brain stimulation at identical rates and currents but did not lever-press for this stimulation. The third experiment examined the effects of lever- pressing for food on an FR8 schedule of reinforcement on DA utilization in the striatum, nucleus accumbens, and olfactory tubercle. Despite high rates of responding, no effects were observed on DOPAC:DA or HVA:DA ratios in these brain regions.

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

“…These animals also consistently exhibited higher maximal response rates during self-stimulation tests. Collectively, these novel results extend previous demonstrations of the involvement of the hippocampal formation in motor output and rewarded behavior [5,9,17,24,48,49] by demonstrating that lesions of this structure can dramatically alter behaviors traditionally ascribed to the mesoaccumbens DA system [2,13,14,29,[43][44][45].…”

“…This was accomplished by using an intra-cranial self-stimulation (ICSS) paradigm, in which the mesolimbic DA system was directly activated by stimulation of the ventral tegmental area (VTA). It has been demonstrated that electrical brain stimulation of the VTA potentiates DA release in the NACC [13,14,[43][44][45]. Electrochemical analyses have revealed that VTA stimulation induced DA release in the NACC increases as a function of increasing current intensity [2].…”

Neuronal Reward and Decision Signals: From Theories to Data

“…Examples are changing visual images, movies, and sexual pictures for which monkeys are willing to exert effort and forego liquid reward (53,124), and the ever increasing prices of paintings (fame and pride may contribute to their reward value). Not surprisingly, the first animal studies eliciting approach behavior by electrical brain stimulation interpreted their findings as discovery of the brain's pleasure centers (398), which were later partly associated with midbrain dopamine neurons (103,155) despite the notorious difficulties of identifying emotions in animals.…”

“…The effect is partly based on activation of VTA and SNpc dopamine neurons (103,155) and involves dopamine release onto D1 receptors in nucleus accumbens (117). Optogenetic activation of midbrain dopamine neurons in rodents elicits learning of place preference, nose poking and lever pressing, and restores learning in a blocking procedure (FIGURE 19, B-D) (2,244,271,562,605,641).…”

Ventral pallidum self-stimulation: a moveable electrode mapping study

“…An impressive number of studies using a variety of methodological approaches, have established that the mesolimbic dopamine (DA) pathway is critically involved in reward function (for reviews, see [4] and [29]). Three distinct behaviors that have been used to assess reward processes are intracranial self-stimulation [ 3,5,7,21 ], drug self-administration [23,24,30,32] and drug-induced place conditioning (for a review, see [27]). These behaviors have been shown to be altered following dopamine manipulations.…”