A role for dopamine D1 receptors of the nucleus accumbens shell in conditioned taste aversion learning - PubMed (original) (raw)

A role for dopamine D1 receptors of the nucleus accumbens shell in conditioned taste aversion learning

S Fenu et al. J Neurosci. 2001.

Abstract

The involvement of dopamine (DA) in conditioned taste aversion (CTA) learning was studied with saccharin or sucrose as the conditioned stimulus (CS) and intraperitoneal lithium as the unconditioned stimulus (US). The dopamine D(1) antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390) (12.5-50 microg/kg, s.c.), given 5 min after the CS, impaired the acquisition of CTA in a paradigm consisting of three or a single CS-lithium association. SCH 23390 failed to impair CTA acquisition given 45 min after, 30 min before, or right before the CS. (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5a-benzo-(d)-naphtho-(2,1b) azepine (SCH 39166) (12.5-50.0 microg/kg, s.c), a SCH 23390 analog that does not bind to 5HT(2) receptors, also impaired CTA. No significant impairment of CTA was obtained after administration of the specific D(2)/D(3) antagonist raclopride (100 and 300 microg/kg, s.c.). The ability of SCH 23390 to impair CTA learning was confirmed by its ability to reduce the conditional aversive reactions to a gustatory CS (sweet chocolate) as estimated in a taste reactivity paradigm. SCH 39166 impaired CTA also when infused in the nucleus accumbens (NAc) shell 5 min after the CS. No impairment was obtained from the NAc core or from the bed nucleus stria terminalis. The results indicate that D(1) receptor blockade impairs CTA learning by disrupting the formation of a short-term memory trace of the gustatory CS and that endogenous dopamine acting on D(1) receptors in the NAc shell plays a role in short-term memory processes related to associative gustatory learning.

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Figures

Fig. 1.

Fig. 1.

Effect of systemic SCH 23390 or saline on saccharin intake conditioned by multiple association with lithium chloride (top panel) or unconditioned (bottom panel). SCH 23390 was given subcutaneously 5 min after saccharin, whereas lithium chloride was given 30 min thereafter. Each bar represents the mean ± SEM of test per trial ratio of saccharin intake in 20 min.+p < 0.05 or++p < 0.005 versus intraperitoneal saline; *p < 0.05 or **p < 0.005 versus lithium.

Fig. 2.

Fig. 2.

Effect of SCH 23390 and SCH 39166 on the intake of saccharin or sucrose either unconditioned or conditioned by lithium chloride. Each bar represents the mean ± SEM of test per trial ratio of saccharin intake in 20 min. a, 6.0 μg/kg, s.c.; b, 12.5 μg/kg, s.c.; c, 25 μg/kg, s.c.; d, 50 μg/kg, s.c.++p < 0.005 versus intraperitoneal saline; *p < 0.05 or **p < 0.005 versus lithium.

Fig. 3.

Fig. 3.

Effect of delay between systemic SCH 23390 and saccharin (top panel) or sucrose (bottom panel) on CTA learning.++p < 0.005 versus intraperitoneal saline; **p < 0.005 versus lithium.

Fig. 4.

Fig. 4.

Effect of SCH 23390 (25 μg/kg, s.c.) on the acquisition of aversive reactions to chocolate induced by a single association with lithium chloride (125 mg/kg, i.p.). Conditioning (trial): hedonic and aversive reactions to chocolate (A, individual; A′, total). Extinction (test): aversive and hedonic reactions to chocolate after saline (open bars) or SCH 23390 (filled bars) plus lithium (B, individual; B′, total). Each bar represents the means ± SEM of hedonic and aversive reactions.a, Rhythmic tongue protrusion; _b,_sniffing; c, paw licks; d, gapes;e, chin rubs; f, paw tread. *p < 0.05 versus subcutaneous saline.

Fig. 5.

Fig. 5.

Effect of infusion of SCH 39166 or saline in the NAc shell, NAc core, LHA, and BNST on saccharin intake conditioned by lithium chloride (80 or 125 mg/kg, i.p; top panel) or unconditioned (bottom panel). Differences between groups were evaluated by two-way ANOVA followed by Tukey's post hoc test.++p < 0.005 versus intraperitoneal saline; *p < 0.05 or **p < 0.005 versus lithium.

Fig. 6.

Fig. 6.

Effect of infusion of SCH 39166 or saline in the NAc shell, NAc core, LHA, and BNST on sucrose intake conditioned by lithium chloride (80 or 125 mg/kg, i.p.; top panel) or unconditioned (bottom panel). Differences between groups were evaluated by two-way ANOVA followed by Tukey's post hoc test.++p < 0.005 versus saline; *p < 0.05 or **p < 0.005 versus lithium.

Fig. 7.

Fig. 7.

Brain sections showing intracerebral injection sites. Section levels are according to Paxinos and Watson (1999).Filled circles, Correct injection sites; filled squares, incorrect injection sites (cc, corpus callosum; Cpu, caudate putamen; _NAc Sh,_nucleus accumbens shell; NAc Co, nucleus accumbens core;LHA, lateral hypothalamic area).

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