High Dose Pimozide Does Not Block Amphetamine-Induced Euphoria in Normal Volunteers

Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum

“…From the present view, orbitofrontal and amygdala reward (and aversive) signals send projections to brain areas that are subject to DA modulation, but also to areas that are not subject to DA modulation, therefore, some (e.g. perceptual) aspects of reward processing occur independent of meso-limbic and nigrostriatal DA activity [18]. Finally, the framework is parsimonious in that it assigns a single role to nigrostriatal and mesolimbic DA neurons: activation under conditions of salient environmental change, and consequent enhancement of glutamate signal-to-noise ratios within dorsal and ventral striatal target sites.…”

“…This view, like a DA/reward signal view, accounts for the disruptive effect of reduced DA transmission on incentive motivation [121,38,60,100,129]. However, in contrast to a DA/ reward signal view, the present framework also accounts for (1) the promiscuous DA response to a wide range of salient and arousing stimuli [57], (2) the fact that disruptions in DA activity can impair animals' abilities to learn about aversive events [1,100], and (3) the observation that disruptions in DA activity impair some, but not all, aspects of reward processing [12,18,90,100]. From the present view, orbitofrontal and amygdala reward (and aversive) signals send projections to brain areas that are subject to DA modulation, but also to areas that are not subject to DA modulation, therefore, some (e.g.…”

“…Salamone and colleagues have shown that ventral striatal DA depletion reduces the ability of food reward to energize animals' behavioral response systems, while leaving some other aspects of reward processing intact [100]. Similarly, the euphoric effects of amphetamine, even at high neuroleptic doses, appear to survive DA antagonist challenge [18].…”

Affective neuroscience of pleasure: reward in humans and animals

“…One line of evidence against a pleasure-causing role is that mesolimbic dopamine neurons may not reliably be activated by pleasure per se but instead by predictive, motivational, or attentional properties rather than hedonic properties of reward stimuli (Carelli 2004;Cheer et al 2007;Redgrave and Gurney 2006;Salamone et al 2007;Schultz et al 1997). Another line of evidence is that, when 'liking' versus 'wanting' are teased apart by brain manipulations, specific manipulation of dopamine signaling either up or down simply fail to shift 'liking' reactions to pleasure reliably in either animals or humans (Berridge 2007;Brauer and De Wit 1997;Cannon and Palmiter 2003;Evans et al 2006;Leyton 2008;Leyton et al 2002;Leyton et al 2005;Peciña et al 2003;Robinson et al 2005;Tindell et al 2005;Volkow et al 2002;Volkow et al 2006). A third line of evidence is that dopamine systems may also be activated by aversive or frankly non-rewarding stimuli, at least tonic dopamine release pulses that last on the order of a few minutes (Ferrari et al 2003;Horvitz 2000;Salamone 1994;Scott et al 2006).…”

Sex Differences and Hormonal Influences on Acquisition of Cocaine Self-Administration in Rats

“…So, another hypothesis comes from considering the actions of progesterone on DA neurotransmission. Although DA systems are hypothesized to be uninvolved in mediating the positive subjective effects (euphoria) of cocaine (Gawin and Kleber, 1986;Brauer and De Wit, 1997;Berridge and Robinson, 1998), they are thought to be important in mediating the reinforcing and incentive motivational effects of cocaine (Yokel and Wise, 1975;Wise and Rompre, 1989;Robinson andBerridge, 1993, 2000;White and Kalivas, 1998;Berridge and Robinson, 1998;Wise and Bozarth, 1987). Importantly, progesterone antagonizes estradiol's enhancement of DA.…”