Dopamine D1 receptors in the nucleus accumbens: involvement in the reinforcing effect of tegmental stimulation

doi:10.1016/0006-8993(88)91095-5

Brain Research

Volume 448, Issue 1, 10 May 1988, Pages 1-6

https://doi.org/10.1016/0006-8993(88)91095-5 Get rights and content

Abstract

Subtypes of dopamine receptors involved in the mechanism of reinforcement were examined. Twenty-five rats were implanted with bipolar electrodes into the ventral tegmental area (VTA) and cannulae into the nucleus accumbens (NAc) or the caudate-putamen complex (CPu). The rats were trained to press a bar to receive VTA stimulation, and dopamine antagonists were injected into the brain while the animals were responding. SCH 23390 (D₁-specific antagonist) injected into NAc ipsilateral to the electrode site suppressed responding, but injections into contralateral NAc or ipsilateral CPu had no effect. Haloperidol was less effective. Sulpiride (D₂-specific antagonist) produced no effect when injected into NAc, though slightly suppressed responding when injected into CPu. The animals that have reduced their response rate after accumbens injection of SCH 23390 responded at a normal rate when the frequency of pulses in the tegmental stimulation was increased, indicating that they were not incapacitated by the D₁ antagonist. These findings suggest that dopamine D₁ receptors in the nucleus accumbens are critically involved in the reinforcement produced by ventral tegmental stimulation.

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Relatively few studies have directly examined the effects on MFB self-stimulation of intracerebral NAcS drug injection. Many of those that have [6,13–18] appeared to assess the drugs’ effects very shortly after the rats were trained on the self-stimulation task, perhaps before they become stable, expert observers and reporters of stimulation reward value. Given the NAcS's association with learning about the behaviors needed to gain rewards (see, e.g., [19]), it is quite possible that these previous studies disrupted the rats’ ability to learn the self-stimulation task and/or to accurately communicate their perceptions of the stimulation's reward effect through their behavior (see [1] for a thorough discussion).
This report compares the effects on medial forebrain bundle self-stimulation of injecting into either the sublenticular central extended amygdala (SLEAc) or nucleus accumbens shell (NAcS) the D1 dopamine receptor blocker SCH23390 or the D2 dopamine receptor agonist quinpirole alone or in combination with the AMPA glutamate receptor blocker NBQX. These manipulations all render affected neurons less excitable and therefore are expected to increase the stimulation pulse frequency required to maintain half-maximal response rate (required frequency, or RF). Injections were made ipsilateral and contralateral to the stimulation site but not bilaterally. Injecting quinpirole alone or in combination with NBQX was more effective in increasing RF than was injecting SCH23390 either alone or with NBQX. Quinpirole alone and in combination with NBQX was more effective when injected into the SLEAc than into the NAcS, and the combination injection was more effective than quinpirole alone, especially when injected into the SLEAc contralateral to the stimulation site. Maximum response rates were only modestly decreased by any drug injection. These data suggest a stronger role in brain stimulation reward for D2/glutamate than D1/glutamate interactions in the extended amygdala.
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Microinjections of SCH 23390 in the ventral tegmental area reduce operant responding under a progressive ratio schedule of food reinforcement in rats
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Specifically, dopamine (DA) neurotransmission in the nucleus accumbens is often implicated in reward-related behavior [1,5,28,30]. The importance of DA in the nucleus accumbens was established by studies demonstrating that disruption of DA neurotransmission in this region attenuates the rewarding effectiveness of conditioned reward [31], brain stimulation reward [15], and self-administered cocaine [17,18]. A role for nucleus accumbens DA in food reward also has been demonstrated; lesions of nucleus accumbens DA terminals [25] disrupt food-rewarded operant responding.
We recently demonstrated that dopamine D1 receptors in the ventral tegmental area (VTA) are involved in intravenous cocaine reward. Here, we investigated whether VTA D1 receptors also are involved in food reward by testing the hypothesis that blockade of dopamine D1 receptors in the VTA attenuates the rewarding effects of food. Eighteen rats, with bilateral cannulae positioned to allow for microinjections in or just dorsal to the VTA, were trained to lever press under a progressive ratio schedule of reinforcement. After stable break points (BPs) were established, the rats received bilateral microinjections of SCH 23390, a D1 receptor antagonist. In Experiment 1, where the reward consisted of 1 food pellet, injections of SCH 23390 (0, 1, 2, or 4 μg/0.5 μl) in the VTA (N = 9) significantly decreased BPs (P < 0.001), while bilateral microinjections dorsal to the VTA (N = 9) did not. In Experiment 2 (N = 6), where the reward consisted of 1 or 2 food pellets, intra-VTA injections of SCH 23390 (0 and 4 μg/0.5 μl) decreased BPs at the 1 food pellet level (P < 0.05), but not at the 2 food pellet level. Thus, the data showed that intra-VTA microinjections of SCH 23390 reduced the rewarding effects of food. This effect was surmountable by increasing food reward, ruling out motoric effects, and did not occur when injections were made dorsal to VTA, eliminating the possibility that the effect was caused by the dorsal diffusion of drug. These data suggest that dendritically released dopamine in the VTA plays a significant role in food reward.
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Research reportDopamine D1 receptors in the nucleus accumbens: involvement in the reinforcing effect of tegmental stimulation

Abstract

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Research report
Dopamine D₁ receptors in the nucleus accumbens: involvement in the reinforcing effect of tegmental stimulation