6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbens d-amphetamine

Abstract

Intra-accumbens d-amphetamine enhances responding for reward-related stimuli (conditioned reinforcers, CRs), whereas intra-caudate d-amphetamine has only weak and variable effects (Taylor and Robbins 1984). The present experiment further examined the involvement of the nucleus accumbens and the role of dopamine (DA) in this effect. Thirsty rats were trained to associate a flash of a light and movement of a dipper (CR) with water. After implantation of permanent guide cannulae aimed at the nucleus accumbens, they were assigned to one of four groups, receiving either bilateral 6-OHDA (4 mg/ml free base in 2 microliters 0.1% ascorbic acid/0.9% saline) or sham (vehicle) infusions into the nucleus accumbens or the caudate nucleus. In the test phase, two novel levers were available. Responding on one lever (CR lever) produced the light and dipper stimuli without water presentation, whereas responding on the other (NCR lever) had no effect. All four groups received four counterbalanced intra-accumbens infusions of d-amphetamine (3, 10, 20 micrograms/2 microliters) or vehicle. On the 5th test day, subjects were pretreated subcutaneously with apomorphine (0.1 mg/kg). Intra-accumbens d-amphetamine in both sham-lesioned groups produced a dose-dependent increase in responding on the CR lever, but no significant change on the NCR lever. No selective increases in responding on either lever were found in animals with 6-OHDA-induced depletion of DA (greater than 80%) in the nucleus accumbens following intra-accumbens d-amphetamine; however, in subjects with DA depletion of the posterior caudate nucleus (greater than 80%).(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…Damage to the hippocampal formation was very similar to that previously described [55]. Histological analyses revealed that all lesioned animals that received kainic acid/colchicine lesions had extensive bilateral damage to the hippocampal formation (see Fig.…”

“…This enhancement in drug-induced activity following extensive hippocampal damage: (i) occurs as a direct function of increased locomotion and not indirectly, from reductions in competing behaviors [59]; (ii) is dependent on the integrity of the mesolimbic dopamine (DA) projection, as 6-OHDA lesions of the NACC block this effect [59]; (iii) occurs specifically in response to pharmacological stimulation of dopamine D2 receptors, which is consistent with the possibility of underlying receptorbased changes [38]; and (iv) corresponds to increases in amphetamine stimulated DA release in the NACC [60]. It is presumed that these changes occur as a function of the degeneration of hippocampal efferents innervating the NACC [4,17,19,20,27,50,51,55,56,63].…”

Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity

“…The discrepancy between the Crean et al study and our study may relate to the difference in sample size (n ¼ 20 in their study vs n ¼ 11 in our study) or the different dose: Crean et al administered 100 mg drinks, associated with an average 84% reduction of TRPÀ levels relative to baseline, while we administered 75 mg drinks, which reduced TRPÀ levels by 61% relative to baseline. Nevertheless, the differential sensitivity of the two measures observed here might be interesting in the context of their association with dissociable underlying corticostriatal circuitries (Taylor and Robbins, 1986;Jentsch and Taylor, 1999;Wyvell and Berridge, 2000;Eagle and Robbins, 2003a, b;Aron et al, 2003;Robbins, 2000).…”

Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

“…The neurobiology of these distinct actions has been well elucidated for cocaine and amphetamine (Taylor and Robbins 1984;Taylor and Robbins 1986;Taylor and Horger 1999;Fletcher and Korth 1999;Fletcher et al 1999;See et al 2001). While basic circuits underlying nicotine reinforcement have been extensively investigated Corrigall et al 1994;Corrigall et al 1992;Corrigall and Coen 1991;Jose Lanca et al 2000;Lanca et al 2000), only limited research has been conducted on the neural underpinnings for the interactions between nicotine and nonpharmacological stimuli (Liu et al 2004;Cohen et al 2005;Paterson et al 2005).…”

“…Infusions of damphetamine into NAcc but not the caudate putamen or thalamus dose-dependently potentiate responding for conditioned stimuli (Taylor and Robbins 1984). Dopaminergic signaling is important for this effect, as suggested by evidence that responding for conditioned reinforcers is accelerated by intra-NAcc dopamine infusions , and reduced by dopamine depletion of the NAcc (Taylor and Robbins 1986;Parkinson et al 2002). Conversely, serotonin depletion augments the potentiation of conditioned reinforcement induced by intra-NAcc amphetamine (Fletcher et al 1999) and in separate studies prior infusion of serotonin (5-HT) or prior activation of 5-HT 1B receptors in the NAcc attenuated the behavioral effects of intra-NAcc amphetamine (Fletcher and Korth 1999).…”