Intra-Accumbens Amphetamine Increases the Conditioned Incentive Salience of Sucrose Reward: Enhancement of Reward “Wanting” without Enhanced “Liking” or Response Reinforcement

“inson (Robinson and Berridge, 1993; Berridge and Robinson, 1998).”

“There were also significant effects on lever pressing for the drug dose factor (F(3,270) 5 3.164; p , 0.05) and the Pavlovian cue presence (F(1,270) 5 30.651; p , 0.001), and there was a significant interaction between cue 3 group (F(1,270) 5 5.671; p , 0.05).”

“First, by making the cue light located on the sucrose lever more attractive, the cue would become a more potent elicitor of approach responses (in a manner similar to autoshaping) ( Brown and Jenkins, 1968; Beagley and Holley, 1977; Rescorla and Cunningham, 1979; Davey et al., 1984; Toates, 1986, 1994; Oscos et al., 1…”

“…processes such as incentive salience, because it measures the ability of a cue to trigger motivation for rewards in the absence of both primary and secondary reinforcement (Rescorla and Solomon, 1967; Toates, 1986; Dickinson and Dawson, 1987; Balleine, 1994; Dickinson and Balleine, 1994).”

“Using the taste reactivity measure of hedonic impact, it was shown that intra-accumbens amphetamine failed to increase positive hedonic reaction patterns elicited by sucrose (i.e., sucrose “liking”) at doses that effectively increase sucrose “wanting.””

“A related experiment investigated whether doses of intra-accumbens amphetamine that increased “wanting” for sucrose would also increase “liking” for sucrose, using the affective taste reactivity technique to measure hedonic impact (Grill and Norgren, 1978; Berridge, 2000a).”

“…processes such as incentive salience, because it measures the ability of a cue to trigger motivation for rewards in the absence of both primary and secondary reinforcement (Rescorla and Solomon, 1967; Toates, 1986; Dickinson and Dawson, 1987; Balleine, 1994; Dickinson and Balleine, 1994).”

“…paradigm (Grill and Norgren, 1978) provides a way of specifically assessing the hedonic impact of a sucrose reward by measuring affective reactions elicited by oral infusions of taste stimuli from human infants, apes, monkeys, or rats (Grill and Berridge, 1985; Berridge, 1996, 2000a) (see Fig.”

“esis suggests that dopamine mediates the hedonic impact of rewards (Wise et al., 1978; Wise, 1985; Gardner and Lowinson, 1993; Volkow et al., 1999).”

“This suggests that amphetamine microinjection induced a modest increase in sensorimotor responsiveness, which is consistent with the hypothesis that mesolimbic dopamine is involved in sensorimotor and integrative functions involved in generating complex responses (Salamone, 1986; Salamone et al., 1997).”

“Thus, our results cannot be explained by an amphetamine-induced enhancement of either primary or secondary reinforcement, although intra-accumbens amphetamine is known to enhance secondary reinforcement when response reinforcement contingencies exist (Taylor and Robbins, 1984; Robbins et al., 1989; Cador et al., 1991;…”

“…of rats to tastes are enhanced by physiological states such as food deprivation or sodium deple- tion (Berridge et al., 1984; Berridge, 1991), similar to the way human subjective ratings of taste palatability are increased by those states (Cabanac, 1979; Beauchamp et al., 1990; Laeng et al., 1993).”

“esis suggests that dopamine mediates the hedonic impact of rewards (Wise et al., 1978; Wise, 1985; Gardner and Lowinson, 1993; Volkow et al., 1999).”

“…paradigm (Grill and Norgren, 1978) provides a way of specifically assessing the hedonic impact of a sucrose reward by measuring affective reactions elicited by oral infusions of taste stimuli from human infants, apes, monkeys, or rats (Grill and Berridge, 1985; Berridge, 1996, 2000a) (see Fig.”

“a food reward as assessed by hedonic taste reactivity (Berridge et al., 1989; Berridge and Robinson, 1998).”

“Reward learning hypotheses suggest that dopamine mediates either response reinforcement or associative predictions of reward (Di Chiara, 1998; McFarland and Ettenberg, 1998; Schultz et al., 1998), and there are still other conceptual alternatives, too (Salamone et al., 1997; Sokolowski and…”

“…paradigm (Grill and Norgren, 1978) provides a way of specifically assessing the hedonic impact of a sucrose reward by measuring affective reactions elicited by oral infusions of taste stimuli from human infants, apes, monkeys, or rats (Grill and Berridge, 1985; Berridge, 1996, 2000a) (see Fig.”

“Reward learning hypotheses suggest that dopamine mediates either response reinforcement or associative predictions of reward (Di Chiara, 1998; McFarland and Ettenberg, 1998; Schultz et al., 1998 ), and there are still other conceptual alternatives, too (Salamone et al., 1997; Sokolowski and Salamone, 1998; Everitt et…”

“According to this theory, food rewards activate two distinctive but interacting systems: a DA-dependent incentive salience system and a DA-independent hedonic system” (Dickinson et al., 2000).”

“…suggests that accumbens dopamine neurotransmission modulates the attribution of incentive salience to reward cues, which triggers a motivational state of “wanting” for both the cue and its associated reward (Berridge and Valenstein, 1991; Robinson and Berridge, 1993; Berridge and Robinson, 1998).”

“, 1998a,b; Ahn and Phillips, 1999), and intra-accumbens microinjection of dopamine (DA) agonists can increase food intake and instrumental performance for food-related cues (Cador et al., 1991; Burns et al., 1993; Sills and Vaccarino, 1996; Swanson et al., 1997).”

“tion (Berridge et al., 1984; Berridge, 1991), similar to the way human subjective ratings of taste palatability are increased by those states (Cabanac, 1979; Beauchamp et al.”

“tion (Berridge et al., 1984; Berridge, 1991), similar to the way human subjective ratings of taste palatability are increased by those states (Cabanac, 1979; Beauchamp et al.”

“These results are compatible with other evidence that sensitization increases the conditioned incentive value of reward-related stimuli (Harmer and Phillips, 1998; De Vries et al., 1999; Fiorino and Phillips, 1999; Taylor and Horger, 1999).”

“…salience Dopaminergic activity in the nucleus accumbens is implicated in motivation for food and other incentives (Hernandez and Hoebel, 1988; Blackburn et al., 1989; Phillips et al., 1993; Mark et al., 1994; Richardson and Gratton, 1996; Di Ciano et al., 1998a,b; Ahn and Phillips, 1999),…”

“…was targeted here because a special role for the shell has been implicated in dopamine activation by palatable food or food cues (Park and Carr, 1998; Bassareo and Di Chiara, 1999) and in the elicitation of feeding behavior (Swanson et al., 1997; Basso and Kelley, 1999; Peciña and Berridge, 2000).”

“As alternative explanations for the role of dopamine in reward, the hedonia hypothesis suggests that dopamine mediates the hedonic impact of rewards (Wise et al., 1978; Wise, 1985; Gardner and Lowinson, 1993; Volkow et al., 1999).”

“, 1998), and there are still other conceptual alternatives, too (Salamone et al., 1997; Sokolowski and Salamone, 1998; Everitt et al., 2000).”

“…of rats to tastes are enhanced by physiological states such as food deprivation or sodium deple- tion (Berridge et al., 1984; Berridge, 1991), similar to the way human subjective ratings of taste palatability are increased by those states (Cabanac, 1979; Beauchamp et al., 1990; Laeng et al., 1993).”

“Dopaminergic activity in the nucleus accumbens is implicated in motivation for food and other incentives (Hernandez and Hoebel, 1988; Blackburn et al., 1989; Phillips et al., 1993; Mark et al., 1994; Richardson and Gratton, 1996; Di Ciano et al., 1998a,b; Ahn and Phillips, 1999), and intra-accumbens microinjection of…”

“Dopaminergic activity in the nucleus accumbens is implicated in motivation for food and other incentives (Hernandez and Hoebel, 1988; Blackburn et al., 1989; Phillips et al., 1993; Mark et al., 1994; Richardson and Gratton, 1996; Di Ciano et al., 1998a,b; Ahn and Phillips, 1999), and intra-accumbens microinjection of…”

“Neither systemic dopamine antagonists (Treit and Berridge, 1990; Peciña et al., 1997) nor depletion of up to 99% of mesolimbic and nigrostriatal dopamine by 6-hydroxydopamine lesions suppress “liking” for a food reward as assessed by hedonic taste reactivity (Berridge et al., 1989; Berridge and…”

“These results are compatible with other evidence that sensitization increases the conditioned incentive value of reward-related stimuli (Harmer and Phillips, 1998; De Vries et al., 1999; Fiorino and Phillips, 1999; Taylor and Horger, 1999).”

“…group, presentation of the CSrandom control cue did not modify the effect of amphetamine on pressing of either the sucrose-associated lever (one-way ANOVA with drug as factor; F(3,31) 5 1.084, p 5 NS) or the nonsucrose control lever (one-way ANOVA with drug as factor; F(3,31) 5 0.270; p 5 NS).”

“For instance, systemic and intracranial injections of opioid agonists or of benzodiazepines have been shown to enhance hedonic palatability using the taste reactivity technique (Treit and Berridge, 1990; Doyle et al., 1993; Peciña and Berridge 1996, 2000).”

“…was targeted here because a special role for the shell has been implicated in dopamine activation by palatable food or food cues (Park and Carr, 1998; Bassareo and Di Chiara, 1999) and in the elicitation of feeding behavior (Swanson et al., 1997; Basso and Kelley, 1999; Peciña and Berridge, 2000).”

“First, by making the cue light located on the sucrose lever more attractive, the cue would become a more potent elicitor of approach responses (in a manner similar to autoshaping) (Brown and Jenkins, 1968; Beagley and Holley, 1977; Rescorla and Cunningham, 1979; Davey et al., 1984; Toates, 1986, 1994; Oscos et al., 19…”

“…processes such as incentive salience, because it measures the ability of a cue to trigger motivation for rewards in the absence of both primary and secondary reinforcement (Rescorla and Solomon, 1967; Toates, 1986; Dickinson and Dawson, 1987; Balleine, 1994; Dickinson and Balleine, 1994).”

“systemic dopamine antagonists (Treit and Berridge, 1990; Peciña et al., 1997) nor depletion of up to 99% of mesolimbic and nigrostriatal dopamine by 6-hydroxydopamine lesions suppress “liking” for”

“…activity in the nucleus accumbens is implicated in motivation for food and other incentives (Hernandez and Hoebel, 1988; Blackburn et al., 1989; Phillips et al., 1993; Mark et al., 1994; Richardson and Gratton, 1996; Di Ciano et al., 1998a,b; Ahn and Phillips, 1999), and intra-accumbens…”

“These results are compatible with other evidence that sensitization increases the conditioned incentive value of reward-related stimuli (Harmer and Phillips, 1998; De Vries et al., 1999; Fiorino and Phillips, 1999; Taylor and Horger, 1999).”

“…and other incentives (Hernandez and Hoebel, 1988; Blackburn et al., 1989; Phillips et al., 1993; Mark et al., 1994; Richardson and Gratton, 1996; Di Ciano et al., 1998a,b; Ahn and Phillips, 1999), and intra-accumbens microinjection of dopamine (DA) agonists can increase food intake and…”

“…lever more attractive, the cue would become a more potent elicitor of approach responses (in a manner similar to autoshaping) (Brown and Jenkins, 1968; Beagley and Holley, 1977; Rescorla and Cunningham, 1979; Davey et al., 1984; Toates, 1986, 1994; Oscos et al., 1988; Berridge, 1996; Tomie, 1996).”

“For instance, systemic and intracranial injections of opioid agonists or of benzodiazepines have been shown to enhance hedonic palatability using the taste reactivity technique (Treit and Berridge, 1990; Doyle et al., 1993; Peciña and Berridge 1996, 2000).”

“…and other incentives (Hernandez and Hoebel, 1988; Blackburn et al., 1989; Phillips et al., 1993; Mark et al., 1994; Richardson and Gratton, 1996; Di Ciano et al., 1998a,b; Ahn and Phillips, 1999), and intra-accumbens microinjection of dopamine (DA) agonists can increase food intake and…”

“Conditioned food preferences based on associative learning also increase positive hedonic taste reactivity patterns, because conditioned stimuli that have been paired with palatable tastes can acquire the ability to enhance hedonic taste reactions (Delamater et al., 1986; Berridge and Schulkin, 1989; Breslin et al., 1…”

“Conditioned food preferences based on associative learning also increase positive hedonic taste reactivity patterns, because conditioned stimuli that have been paired with palatable tastes can acquire the ability to enhance hedonic taste reactions (Delamater et al., 1986; Berridge and Schulkin, 1989; Breslin et al., 1…”

“Thus, our results cannot be explained by an amphetamine-induced enhancement of either primary or secondary reinforcement, although intra-accumbens amphetamine is known to enhance secondary reinforcement when response reinforcement contingencies exist (Taylor and Robbins, 1984; Robbins et al., 1989; Cador et al., 1991;…”

“, 1998a,b; Ahn and Phillips, 1999), and intra-accumbens microinjection of dopamine (DA) agonists can increase food intake and instrumental performance for food-related cues (Cador et al., 1991; Burns et al., 1993; Sills and Vaccarino, 1996; Swanson et al., 1997).”

“First, by making the cue light located on the sucrose lever more attractive, the cue would become a more potent elicitor of approach responses (in a manner similar to autoshaping) (Brown and Jenkins, 1968; Beagley and Holley, 1977; Rescorla and Cunningham, 1979; Davey et al., 1984; Toates, 1986, 1994; Oscos et al., 19…”

“Dopamine activation or suppression specifically modulates the strength of this cue-triggered burst of 'wanting' motivation, which decays away soon after the reward cue is removed, only to reappear again when the cue is reencountered later (Dickinson et al. 2000; Wyvell and Berridge 2000, 2001).”

“An encounter with a CS for a reward also triggers ‘wanting’ for its own associated UCS, presumably via transfer of incentive salience to associatively linked representations of the absent reward [34,47,48].”

“Thus, for example, dopamine activity appears to be critical for general transfer, which is abolished by DA antagonists and local inactivation of the VTA (Dickinson et al, 2000; Murschall and Hauber, 2006), whereas amphetamine-induced sensitization can enhance it (Wyvell and Berridge, 2000).”

“, higher runway performance of hyperdopaminergic mutant mice; higher peaks of cue-triggered effort to obtain sucrose reward, increases in reward consumption, and higher peaks of neural firing in NAc-VP circuits that encode cuetriggered ‘‘wanting’’) (Peciña and Berridge, 2013; Peciña et al., 2003; Smith et al., 2011; W…”

“Originally surprising were findings that mesocorticolimbic DA manipulations do not change “liking” for the taste of sucrose (Peciña et al., 1997; Wyvell and Berridge, 2000), despite their role in incentive “wanting” for these and other rewards.”

“When incentive salience is attributed to a reward stimulus representation, it makes that stimulus attractive, attention grabbing, and a target for many Bindra–Toatesstyle goal-directed strategies [13,126,194].”

“There are many aspects of reward, including: hedonic (liking) and incentive (wanting) valu”

“Simultaneous presence of cues and hunger states (or drug states) can be needed to reveal amplification of incentive salience in neural and behavioral experiments [20,134], and may be important to reveal dopamine increases and related limbic activations [35,135,136].”

“…Parkinson et al., 1999; Parkinson et al., 2000b) and its role in instrumental Page 12 of 47 Ac ce pt ed M an us cr ip t 12 behaviour may be best described as providing a stimulus-induced motivational influence on the performance (Balleine, 2005; Parkinson et al., 2000a; Wyvell and Berridge, 2000).”

“…suggested to mediate Pavlovian (stimulus-outcome; S-O) associative processes and to direct both approach and instrumental (response-outcome; R-O) behaviour (Brown and Braver, 2005; Cador et al., 1991; Cardinal et al., 2002; Robbins et al., 1989; Taylor and Robbins, 1984; Wyvell and Berridge, 2000).”

“To date, research dissociating these two systems has focused on subcortical and neurotransmitter systems rather than on cortical areas (Pecina & Berridge 2005, Wyvell & Berridge 2000).”

“Similar elevations of 'wanting' without 'liking' have also been produced in ordinary rats by amphetamine-induced elevation in dopamine release, and by long term drug-sensitization of mesolimbic systems (Peciña et al., 2003; Tindell et al., 2005; Wyvell and Berridge, 2000).”

“These cues promote motor behavior to obtain food reward (Wyvell and Berridge, 2000).”

“…of instrumental behavior by pavlovian stimuli is amplified by increased DA in the NAc shell in a way that is itself subject to sensitization (Wyvell and Berridge, 2000, 2001), perhaps representing the sensitized conditioned incentive salience that underlies drug “wanting,” the process at…”

“…in re-encounter if dopamine levels in nucleus accumbens are elevated above normal at that moment by a drug such as amphetamine or by neural sensitization induced by previous exposures to amphetamine or related drugs (Wyvell & Berridge, 2000, 2001; Tindell et al., 2005; Smith et al., 2011).”

“This accumbens ‘liking’ subsystem is embedded in larger mesolimbic neural systems related to ‘wanting’ for food and other types of reward (Berridge & Robinson, 1998; Everitt et al., 1999; Kelley, 1999; Panksepp, 1998; Wyvell & Berridge, 2000).”

“Observation of increased eating without enhanced hedonic impact appears somewhat similar to dissociations of food “wanting” from “liking” produced by other manipulations of mesolimbic function (Berridge and Valenstein, 1991; Reynolds and Berridge, 2002; Wyvell and Berridge, 2000; Peciña et al., 2003).”

“Both systemic dopamine antagonist injection (Dickinson et al. 2000) and inactivation of the VTA (Murschall & Hauber 2006) reduced lever pressing in response to the CS. Conversely, lever pressing to the CS was potentiated by NAc amphetamine injection (Wyvell & Berridge 2000).”

“…Swanson et al., 1997; Schildein et al., 1998), conditioned approach responses (Taylor and Robbins, 1986; Kelley and Delfs, 1991; Burns et al., 1993; Wolterink et al., 1993; Parkinson et al., 1999; Wyvell and Berridge, 2000) and anticipatory sexual behaviors (Everitt et al., 1989; Everitt, 1990).”

“…energize ongoing instrumental actions, as indicated by the Pavlovian-to-instrumental transfer effect (e.g., Dickinson et al., 2000; Lovibond, 1983; Wyvell and Berridge, 2000); and (3) they can reinforce the learning of new instrumental actions; that is, they can act as conditional reinforcers…”

“Our results are reminiscent of similar reports of increased wanting accompanied by slightly decreased “liking” produced by amphetamine microinjection in the nucleus accumbens and by electrical stimulation of the medial forebrain bundle (Berridge and Valenstein, 1991; Wyvell and Berridge, 2000).”

“Moreover, intra-NAc shell infusions of amphetamine enhanced the motivational effects of Pavlovian conditioned stimuli on instrumental behavior (Pavlovian-to-instrumental transfer, a form of Pavlovian arousa”

“Intra-accumbens amphetamine injections were shown to facilitate Pavlovian-to-instrumental transfer [47]; nucleus accumbens lesions impaired this effect [46].”

“…al., 1999), and by the DA receptor antagonist pimozide (Dickinson et al., 2000), whereas intra-accumbens infusions of D-amphetamine potentiate the response-incremental effects of a pavlovian CS1 (Wyvell and Berridge, 2000), much as they potentiate conditioned reinforcers (Taylor and Robbins, 1984).”

“Using this paradigm, Wyvell and Berridge (2000) showed that mesolimbic activation caused by an amphetamine microinjection into the nucleus accumbens selectively increased cue-triggered wanting for sucrose reward, without enhancing either response reinforcement or sucrose “liking.””

“Third, given dopamine’s established positive correlation with approach and PIT [87,88], we expect genetic polymorphisms that boost DA levels, such as the SLC6A3 polymorphism of the dopamine transporter [89], to increase the impact of appetitive Pavlovian stimuli on approach.”

“As an initial step in this direction, we hope that the framework discussed here will serve as a useful starting point for future investigation.”

“…have positively valenced motivational effects on behavior, including affective reactions to taste for opioids, even when administered at shell sites that caused negative or mixed effects here (Bakshi and Kelley, 1993; Peciña and Berridge, 2000; Wyvell and Berridge, 2000; Zhang and Kelley, 2000).”

“This distinction might be related to the “wanting” without “liking” evoked by dopamine and GABA manipulations in nucleus accumbens, which appear to be mediated by motivational incentive salience mechanisms that are separable from hedonic impact mechanisms (Berridge and Valenstein, 1991; Wyvell and Berridge, 2000; Reyn…”

“Berridge and Kringelbach ( 2008 ) and Wyvell and Berridge ( 2000 ) draw a distinction between “liking” and “wanting”.”

“Conditioned, or cue-triggered, wanting is measured by using conditioned incentive paradigms (Wyvell & Berridge, 2000).”

“In this way, the MO model could provide a methodological platform from which ‘irrational wanting’ (Wyvell and Berridge, 2000) might be simulated in humans.”

“Furthermore, large reductions or exaggerations in dopamine levels induced within the mesocorticolimbic system do not seem to alter hedonic reactions to natural rewards (Berridge et al. , 1989, Kaczmarek and Kiefer, 2000, Pecina et al. , 1997, Wyvell and Berridge, 2000).”

“…or by drug-induced neural sensitization interposed between CS–UCS training and CS reencounter (DiFeliceantonio & Berridge, 2012; Pecina & Berridge, 2013; Smith, Berridge, & Aldridge, 2011; Tindell, Berridge, Zhang, Peciña, & Aldridge, 2005; Vezina & Leyton, 2009; Wyvell & Berridge, 2000).”

“Although specifically reducing NAc dopamine function has not yet been shown to reduce the baseline PIT effect, administration of a systemic dopamine antagonist reduces PIT (Dickinson et al. 2000), as does inactivation of the ventral tegmental area (VTA), the midbrain structure containing dopamine neurons that project…”

“Furthermore, amphetamine microinjections targeted at the NAcc shell have been shown to enhance PIT (Wyvell & Berridge, 2000), just as the shell has been shown to mediate the dopaminergic enhancement of conditioned reinforcement (Everitt & Robbins, 1992).”

“Indeed, infusion of DA receptor agonists into the NAcc increased the ability of a Pavlovian stimulus to enhance instrumental responding without influence on the hedonic value of the reward (Wyvell and Berridge, 2000), whereas infusion of DA receptor agonists into the NAcc increased responding for a conditioned stimulu…”

“Lastly, and in contrast to the hedonic effects of mu opioid receptor stimulation, microinjections of the GABA antagonist bicuculline stimulated food intake throughout the entire VP, but never altered taste reactivity orofacial patterns at any VP site (Smith and Berridge, 2005).”

“These latter reactions have been proposed to reflect the hedonic impact of both foods and the CS’s that predict food delivery and have been reported to be unaffected by lesions of the striatal DA input [23], the administration of pimozide [100] or the facilitation of DA transmission by either microinjection of ampheta…”

“For example, the presentation of a drug-associated CS to animals can induce large conditioned increases in NAc DA [82,141], suggesting that DA in the NAc is involved in cue-controlled drug seeking [308] through interactions with limbic afferents to the NAc [81,83].”

“But the enhanced "wanting" for food is not accompanied by increased "liking," as evidenced by the microinjection's failure to increase positive hedonic patterns of behavior elicited from the rats by a sweet taste (Wyvell & Berridge, 2000 ).”

“hedonic taste reaction patterns at doses that augmented lever pressing induced by presentation of a Pavlovian conditioned stimulus for food delivery (Wyvell and Berridge 2000).”

“…measure of attention capture (Anderson et al., 2011) parallels the paradigm of operant extinction used to measure wanting in animals (e.g., Wyvell and Berridge, 2000), and so we predicted it would correlate inversely with breath counting accuracy – supporting convergent validity – and do…”

“In PIT, the phasic peaks of cue-triggered ‘wanting’ are manifest as a burst of pressing by the rat on a lever that previously earned sucrose reward: these peaks were dynamically enhanced by microinjection of amphetamine directly into the nucleus accumbens, or by sensitizing drug binges given weeks earlier [72,73] (Fig…”

“Similarly, amphetamine injection into nucleus accumbens can increase the leverpressing for sucrose that is triggered by cues that have been associated with sucrose outside the context of the instrumental task (Wyvell and Berridge, 2000).”

“value (liking) decreases, while anticipatory reward increases [81].”

“Consistent with this view, Ahn and Philips [2] observed that NAcc DA release appears to correspond to Pavlovian incentive processes, and several studies have now provided supporting evidence for the view that NAcc DA contributes to the way in which motivationally significant Pavlovian stimuli can direct and invigorate…”

“…unlikely because using identical procedures we have shown robust effects of amphetamine infusions into the shell to increase responding with conditioned reinforcement (Parkinson et al. 1999), while similarly large effects were also seen by Wyvell and Berridge (2000), again using vertical cannulae.”

“…paradigm that amphetamine microinjection in this same caudal shell site increases appetitive cue-triggered bar pressing for a sucrose reward (Wyvell and Berridge, 2000) and with findings of greatest reward effects in place preference and brain self-stimulation paradigms after histamine…”

“Later studies in our lab went on to identify various psychological signature features of dopamine-mediated ‘wanting’ or incentive salience, which will be described later (Wyvell and Berridge, 2000; Peciña et al., 2003; Smith et al., 2011; Pecina and Berridge, 2013).”

“Recent investigations show that lateral hypothalamic neurons expressing orexin (77, 199) and other transmitters such as neurotensin (101, 107) provide modulatory input to midbrain dopamine neurons well known to be crucial players in translating motivation into action (10, 14, 22, 42, 77, 91, 148, 194, 196).”