Pharmacological evidence for a role of D2 dopamine receptors in the defensive behavior of the mouse

In this study the role of the DA system in the expression of defensive behavior of the mouse was investigated. C57BL/6 mice subjected to three daily defeat experiences (24 h apart) exhibited an increase of defensive behaviors (upright and sideways postures and escape) as well as a decrease of activity and a decrease of social investigation compared with undefeated mice (controls) when confronted with nonaggressive Swiss mice 24 h after the last aggressive confrontation. The selective D2 DA receptor antagonist (-)-sulpiride administered before confrontation with nonaggressive opponents (fourth day) dramatically decreased defensive behaviors and produced an increase of social investigation. The selective D1 DA receptor antagonist SCH 23390 did not affect either defence or social investigation. In further experiments the behavioral effects of the selective D1 agonist SKF 38393 and of the selective D2 agonist LY171555 on naive C57BL/6 mice interacting with nonaggressive opponents of the same strain were assessed. SKF 38393 in doses up to 30 mg/kg did not produce any significant behavioral changes while LY171555 produced a clear-cut dose-dependent increase of defensive behavior as well as a decrease of social investigation and activity and an increase of immobility. The behavioral profile produced by the D2 agonist did not differ from that produced by defeat experiences. These results indicate that D2 receptors play a major role in the expression of defensive behavior in the mouse. The hypothesis that alteration in D2 receptor functioning may produce hyperdefensiveness possibly due to altered perceptive processes is discussed.     

Modulatory influence of dopamine receptors on consolidation of object recognition memory

The role of dopamine receptors in regulating the formation of recognition memory remains poorly understood. Here we show the effects of systemic administration of dopamine receptor agonists and antagonists on the formation of memory for novel object recognition in rats. In Experiment I, rats received an intraperitoneal (i.p.) injection of vehicle, the selective D1 receptor agonist SKF38393 (1.0 and 5.0mg/kg), or the D2 receptor agonist quinpirole (1.0 and 5.0mg/kg) immediately after training. In Experiment II, rats received an injection of vehicle, the dopamine receptor antagonist SCH23390 (0.1 and 0.05 mg/kg), or the D2 receptor antagonist raclopride (0.5 and 0.1mg/kg) before training, followed by an injection of vehicle or the nonselective dopamine receptor agonist apomorphine (0.05 mg/kg) immediately after training. SKF38393 at 5mg/kg produced an enhancement of novel object recognition memory measured at both 24 and 72 h after training, whereas the dose of 10mg/kg impaired 24-h retention. Posttraining administration of quinpirole did not affect 24-h retention. Apomorphine enhanced memory in rats given pretraining raclopride, suggesting that the effect was mediated by selective activation of D1 receptors. The results indicate that activation of D1 receptors can enhance recognition memory consolidation. Importantly, pharmacological activation of D1 receptors enhanced novel object recognition memory even under conditions in which control rats showed significant retention.     

Modulation of recognition and temporal order memory retrieval by dopamine D1 receptor in rats

The present study examines the effects of SKF 81297, a selective D1 agonist, on information retrieval in recognition and temporal order memory for objects, using three different tasks. Separate groups of rats were trained in each task and then given an intraperitoneal injection of saline or the D1 agonist (0.03, 0.3 mg/kg), before the memory testing trial in an object recognition, object location, and object temporal order memory tasks. We show that SKF 81297, at high dose (0.3 mg/kg), facilitates information retrieval after a long delay (4 h) in the three memory tasks whereas both high and low doses of D1 agonist impair recognition memory after a short delay (15 min). These results indicate a significant role of dopamine D1 receptors in recognition memory for both familiarity and place of objects in addition to object temporal order memory.     

Glucocorticoid-induced impairment of long-term memory retrieval in rats: an interaction with dopamine D2 receptors

This study investigated glucocorticoid-dopaminergic interactions in modulating retrieval of long-term memory in an inhibitory avoidance task. Young adult male rats were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On the retention test given 48 h after training, the latency to re-enter the dark compartment of the apparatus was recorded. Systemically administered corticosterone (1 or 3 mg/kg) given to rats 30 min before retention testing impaired their memory retrieval, but the lower dose was more effective than the higher one. Administration of the dopamine (DA) D2 receptor antagonist sulpiride (6 or 20 mg/kg) 30 min before corticosterone attenuated the impairing effects of corticosterone (1 mg/kg) on memory retrieval. Administration of the DA D1 receptor antagonist SCH23390 (25 or 50 microg/kg) had no effect on corticosterone-induced impairment of memory retrieval. Further, applied doses of sulpiride or SCH23390 alone were ineffective in modulating memory retrieval. These findings provide evidence for the existence of an interaction between glucocorticoids and DA D2 receptor on memory retrieval process.     

D1/D5 dopamine receptors modulate spatial memory formation

We investigated the effect of the intra-CA1 administration of the D1/D5 receptor antagonist SCH23390 and the D1/D5 receptor agonist SKF38393 on spatial memory in the water maze. When given immediately, but not 3h after training, SCH23390 hindered long-term spatial memory formation without affecting non-spatial memory or the normal functionality of the hippocampus. On the contrary, post-training infusion of SKF38393 enhanced retention and facilitated the spontaneous recovery of the original spatial preference after reversal learning. Our findings demonstrate that hippocampal D1/D5 receptors play an essential role in spatial memory processing.     

Influence of intracerebroventricular administration of dopaminergic drugs on morphine state-dependent memory in the step-down passive avoidance test

The effects of dopaminergic drugs on morphine state-dependent memory of passive avoidance task were examined in mice. Pre-training administration of morphine (5mg/kg) led to state-dependent learning with impaired memory retrieval on the test day which was reversed by pre-test administration of the same dose of the opiate. The pre-test intracerebroventricular (i.c.v.) administration of the dopamine D1 receptor agonist (SKF38393), dopamine D2 receptor agonist (quinpirole) and dopamine D2 receptor antagonist (sulpiride) not only reversed the effect of pre-training morphine treatment, but also increased this action of the drug. Furthermore, the pre-test i.c.v. administration of dopamine D1 receptor antagonist (SCH23390) prevented the restoration of memory by morphine. In conclusion, the morphine-induced recovery of memory, on the test day, seems to be induced, at least in part, through dopamine receptors.     

Effects of anandamide and morphine combinations on memory consolidation in cd1 mice: involvement of dopaminergic mechanisms

In the present research the interaction between the endogenous ligand for the cannabinoid CB1 receptor anandamide (arachidonylethanolamide) and morphine in memory consolidation was investigated. Four sets of experiments were carried out with CD1 mice tested in a one-trial inhibitory avoidance task. The drugs were administered intraperitoneally after training of the animals in the apparatus. In the first set of experiments morphine (0.3 or 0.5, but not 0.15mg/kg) or anandamide (3 or 6 but not 1.5mg/kg) dose-dependently impaired memory consolidation. In the second set of experiments the administration of an otherwise ineffective dose of anandamide (1.5mg/kg) enhanced the memory impairment exerted by morphine (0.3 and 0.5mg/kg) when the drugs were injected immediately after training. In the third set of experiments the combined treatments of anandamide (1.5mg/kg) and morphine (0.5mg/kg) 2h after training were ineffective showing that the effects observed on performance following immediate posttraining administration of anandamide and morphine combinations were reflecting direct influences on memory consolidation. In the fourth set of experiments otherwise ineffective doses of the D1 DA receptor agonist SKF 38393 or the D2 DA receptor agonist LY 171555 antagonized the memory impairment produced by anandamide and morphine in combination, suggesting a possible involvement of dopaminergic mechanisms.     

Roles of dopamine D1 and D2 receptors in the acquisition and expression of fat-conditioned flavor preferences in rats

Sugars and fats elicit innate and learned flavor preferences with the latter mediated by flavor-flavor (orosensory) and flavor-nutrient (post-ingestive) processes. Systemic dopamine (DA) D1 (SCH23390: SCH) and D2 (raclopride: RAC), but not opioid antagonists blocked the acquisition and expression of flavor-flavor preferences conditioned by sugars. In addition, systemic D1, but not D2 or opioid antagonists blocked the acquisition of flavor-nutrient preferences conditioned by intragastric (IG) sugar infusions. Given that DA antagonists reduce fat intake, the present study examined whether systemic D1 or D2 antagonists altered the acquisition and/or expression of conditioned flavor preferences (CFP) produced by pairing one novel flavor (CS+, e.g., cherry) with a 3.5% corn oil (CO: fat) solution relative to another flavor (CS-, e.g., grape) paired with a 0.9% CO solution. In an expression study, food-restricted rats were trained to drink either flavored 3.5% or 0.9% CO solutions on alternate days. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO solutions occurred 0.5h after systemic administration of vehicle (VEH), SCH (50-800 nmol/kg) or RAC (50-800 nmol/kg). The rats displayed a robust CS+ preference following VEH treatment (87-88%) the expression of which was attenuated by treatment with moderate doses of RAC, and to a lesser degree, SCH. In an acquisition study, six groups of rats received VEH, SCH (25, 50, 200 nmol/kg) or RAC (50, 200 nmol/kg) 0.5 h prior to 1-bottle training trials with CS+ flavored 3.5% and CS- flavored 0.9% (CS-) CO solutions. A seventh Limited VEH group was trained with its training intakes limited to that of the SCH and RAC groups. Subsequent two-bottle tests were conducted with the CS+ and CS- flavors presented in 0.9% CO without injections. Significant and persistent CS+ preferences were observed in VEH (75-82%), Limited VEH (70-88%), SCH25 (75-84%), SCH50 (64-87%), SCH200 (78-91%) and RAC200 (74-91%) groups. In contrast, the group trained with RAC50 displayed a significant initial CS+ preference (76%) which declined over testing to 61%. These data indicate limited DA D1 and D2 receptor signaling involvement in the expression and acquisition of a fat-CFP relative to previous robust effects for sugar-CFP.     

Strain-dependent effects of post-training dopamine receptor agonists and antagonists on memory storage in mice.

Post-training administration of the selective D1 or D2 agonists SKF 38393 and LY 171555 dose dependently impairs retention of an inhibitory avoidance response in DBA/2 mice. In agreement, the selective D1 or D2 antagonists SCH 23390 and (-)-sulpiride improve retention. These effects are opposite to those observed in the C57BL/6 strain, as previously reported. Moreover, B6D2F1 hybrids present a response to SKF 38393, LY 171555, SCH 23390, and (-)-sulpiride that parallels that of the C57BL/6 strain, thus suggesting that the neural mechanisms underlying the effects of DA agonists or antagonists on memory processes may be inherited through a dominant mode of inheritance.     

The role of dopamine in reinforcement: changes in reinforcement sensitivity induced by D1-type, D2-type, and nonselective dopamine receptor agonists

Dose-dependent changes in sensitivity to reinforcement were found when rats were treated with low, moderate, and high doses of the partial dopamine D1-type receptor agonist SKF38393 and with the nonselective dopamine agonist apomorphine, but did not change when rats were treated with similar doses of the selective dopamine D2-type receptor agonist quinpirole. Estimates of bias did not differ significantly across exposure to SKF38393 or quinpirole, but did change significantly at the high dose of apomorphine. Estimates of goodness of fit (r2) did not change significantly during quinpirole exposure. Poor goodness of fit was obtained for the high doses of SKF38393 and apomorphine. Decrements in absolute rates of responding were observed at the high dose of quinpirole and at the moderate and high doses of SKF38393 and apomorphine. Changes in r2 and absolute responding may be due to increases in stereotyped behavior during SKF38393 and apomorphine exposure that, in contrast to quinpirole, were distant from the response lever. The present data provide evidence that sensitivity to reward is affected more strongly by dopamine D1-like receptors rather than D2-like receptors, consistent with evidence from other studies investigating consummatory dopamine behavior and the tonic/phasic dopamine hypothesis.     

慢性应激性抑郁发生中大鼠眶额叶多巴胺D1受体对谷氨酸及其NMDA受体的调节

本文旨在探讨慢性应激性抑郁发生过程中眶额叶多巴胺D1受体对谷氨酸(glutamic acid, Glu)及其N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid, NMDA)受体的NR2B亚基的影响。实验通过建立慢性不可预见性温和应激(chronic unpredictable mild stress, CUMS)抑郁模型, 结合眶额叶微量注射多巴胺D1受体激动剂SKF38393和多巴胺D1受体拮抗剂SCH23390, 运用糖水偏爱测试、悬尾实验和敞箱实验等方法检测动物的行为表现, 采用高效液相色谱法(high-performance liquid chromatography, HPLC)和蛋白质免疫印迹法(Western blot, WB)来检测眶额叶内谷氨酸、多巴胺含量及NR2B和多巴胺D1受体的表达。结果显示, 与对照组相比, CUMS组大鼠表现出明显的抑郁样行为变化, 且眶额叶多巴胺含量降低, 其D1型受体表达降低, 谷氨酸含量升高, 其NMDA受体的NR2B亚基也明显上调; 注射SKF38393后可明显改善应激引起的抑郁样行为, 且眶额叶谷氨酸含量显著下降, NMDA受体的NR2B亚基表达也有所降低; 正常大鼠注射多巴胺D1受体拮抗剂SCH23390, 大鼠表现出和CUMS模型组相似的抑郁样行为, 且眶额叶谷氨酸含量升高, 其NMDA受体的NR2B亚基也明显上调。以上结果表明, 慢性不可预见性应激可能使眶额叶多巴胺释放减少, 从而使谷氨酸过量释放, NMDA受体过度激活, 导致抑郁发生。多巴胺抗抑郁作用是通过D1型受体抑制谷氨酸及其NMDA受体NR2B亚基表达来实现。     

Microinjections of the dopamine D2 receptor antagonist sulpiride into the medial prefrontal cortex attenuate glucocorticoid-induced impairment of long-term memory retrieval in rats

We recently reported that blockade of dopamine (DA) D2 receptors attenuated deficits in long-term memory retrieval induced by a systemic injection of corticosterone, but the anatomical sites of such interaction were not known. In this study, we investigated whether the DA D2 receptors located in the medial prefrontal cortex (mPFC) may play a role in the impairing effects of glucocorticoids on the memory retrieval process. Young adult male rats were trained in a one trial inhibitory avoidance task (0.5 mA, 3s footshock). On the retention test given 48 h after training, the latency to re-enter the dark compartment and the time spent in light compartment of the apparatus were recorded. Systemically administered corticosterone (1mg/kg) given to rats 30 min before retention testing impaired their memory retrieval. Bilateral microinjections of the DA D2 receptor antagonist sulpiride (10 or 100 ng/0.5 microl per side) into the mPFC 30 min before corticosterone administration attenuated the glucocorticoid-induced impairment of memory retrieval. Furthermore, applied doses of sulpiride alone were ineffective in modulating memory retrieval. These findings indicate that D2 receptors located in the mPFC play an important role in mediating the impairing effects of glucocorticoids on memory retrieval.     

Strain-dependent interactions between MK-801 and cocaine on retention of C57BL/6 and DBA/2 mice tested in a one-trial inhibitory avoidance task: involvement of dopaminergic mechanisms

Two sets of experiments were carried out with C57BL/6 (C57) and DBA/2 (DBA) mice tested in a one-trial inhibitory avoidance task. In the first set C57 and DBA mice were injected posttraining with saline or with the D1 DA receptor antagonist SCH 23390 and then with saline, cocaine (5 mg/kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Cocaine enhanced retention in the C57 strain and impaired it in the DBA strain, and MK-801 potentiated the effects of cocaine in both strains. Furthermore, pretreatment with SCH 23390 completely antagonized the potentiation of the effects of cocaine exerted by MK-801. In the second set of experiments mice belonging to these same two strains were injected posttraining with vehicle or with the D2 DA receptor antagonist (-)-sulpiride and then with saline, cocaine (5 mg/kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Pretreatment with the D2 DA receptor antagonist completely antagonized in both strains the potentiation of the effect of cocaine exerted by MK-801. The results of the present research show that the noncompetitive NMDA receptor antagonist MK-801 enhances the effect of cocaine on retention performance in C57 and DBA mice and that dopaminergic mechanisms are involved in this potentiation.     

Effects of (+) SKF 10,047, a sigma-1 receptor agonist, on anxiety,tested in two laboratory models in mice

Recently, sigma-1 receptor modulators have been considered drugs with an interesting therapeutic potential for the treatment of anxiety. However, there is no clear information in preclinical studies about the possible effects of sigma-1 ligands on anxiety in experimental animal models. Therefore, the present study examined the effects of (+)SKF 10,047 (2-8 mg/kg, ip), a sigma-1 agonist, on anxiety, tested in two classical laboratory models (social interaction test and elevated plus maze). (+)SKF 10,047 (8 mg/kg) produced a significant decrease of social investigation in the "social interaction test", whereas in the "elevated plus maze", the drug (4 and 8 mg/kg) provoked a significant reduction in the number of entries into open arms, as well as in the time spent in this area, as compared with the control group, without affecting motor activity. Overall, these findings indicate that (+)SKF 10,047 exhibits an anxiogenic-like profile in mice. It is suggested that anxiogenic effects of this sigma-1 ligand could be related to its potent ability to modulate diverse neurotransmitter systems involved in anxiety regulation.     

Cholinergic-dopaminergic interactions in cognitive performance

Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.     

Opioid peptidergic systems modulate the activity of beta-adrenergic mechanisms during memory consolidation processes

Post-training administration of the opioid receptor antagonist naloxone (0.1 mg/kg) facilitated 48-hr retention, in mice, of a one-trial step-through inhibitory avoidance response. The naloxone-induced memory facilitation was blocked in animals given the selective brain-noradrenergic neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) (50.0 mg/kg, ip) 7 days before training. Pretreatment with the norepinephrine-uptake inhibitor desmethylimipramine (10.0 mg/kg, ip, 30 min), but not with the serotonin-uptake inhibitor fluoxetine (5.0 mg/kg, ip, 30 min), prevented this antagonism. The simultaneous administration of the central beta-adrenoceptor blocker l-propranolol (2.0 mg/kg, ip), also blocked the effects of naloxone on memory. The effects of naloxone were not blocked by d-propranolol (2.0 mg/kg, ip), the peripheral beta-adrenoceptor blocker sotalol (2.0 mg/kg, ip), the alpha-adrenoceptor blocker phenoxybenzamine (10.0 mg/kg, ip), or the predominantly peripheral alpha-adrenoceptor blocker phentolamine (10.0 mg/kg, ip). These findings suggest that central beta-adrenergic mechanisms are involved in the effects of naloxone on memory. Naloxone (0.1 mg/kg, ip) potentiated the effects of the central beta-adrenoceptor agonist clenbuterol (0.001-1.00 mg/kg, ip), which, when administered alone, facilitates or impairs retention as a function of the dose injected. The simultaneous administration of beta-endorphin (0.1 micrograms/kg, ip) exerted effects opposite to those elicited by naloxone, that is, shifted the dose-response curve of clenbuterol to the right. Considered together, these findings are consistent with the view that the facilitatory action of naloxone on memory results from the release of central beta-adrenergic mechanisms from an inhibition induced by opioid peptides released during or immediately after training.     

Localized intracaudate dopamine D2 receptor activation during the post-training period improves memory for visual or olfactory conditioned emotional responses in rats.

Rats with cannulas aimed at the posteroventral (PV) or ventrolateral (VL) areas of the caudate nucleus were trained on a conditioned emotional response (CER) task. Post-training microinjections of the indirect catecholamine agonist, d-amphetamine (5 micrograms), or of the dopamine D2 receptor agonist, LY171555 (1 microgram), into the PV area improved retention of a CER with a visual CS, but had no effect on a CER with an olfactory CS. Post-training injections of the same two drugs into the VL area improved retention of a CER with an olfactory CS, but had no effect on a CER with a visual CS. Post-training injections of the dopamine D1 receptor agonist, SKF38393 (0.5, 1.0, 2.0 micrograms), into either site had no effects on either CER. These findings suggest that different areas of the caudate nucleus mediate acquisition of CERs with different CSs, possibly implicating the topographically organized corticostriatal innervation in the acquisition of certain types of memories in the caudate nucleus. The findings also suggest that dopamine D2 receptors in the caudate nucleus are involved in the acquisition of these CERs.     

Memory-modulatory effects of centrally acting noradrenergic drugs: possible involvement of brain cholinergic mechanisms.

Post-training administration of the centrally acting muscarinic agonist oxotremorine (50.0 microgram/kg, ip) facilitated 48-hr retention, in mice, of a one-trial step-through inhibitory avoidance response. Oxotremorine-induced memory facilitation was not prevented by the simultaneous post-training administration of the central beta-adrenoceptor antagonist propranolol (2.0 mg/kg, ip). In contrast, post-training administration of atropine (0.5 mg/kg, ip), but not methylatropine (0.5 mg/kg, ip), completely prevented the facilitatory effects of the central beta-adrenoceptor agonist clenbuterol (30.0 micrograms/kg, ip) on retention. Low subeffective doses of clenbuterol (3.0 micrograms/kg, ip) and oxotremorine (6.25 or 12.5 micrograms/kg, ip) potentiated their effects and facilitated retention when given simultaneously immediately post-training. These results suggest that clenbuterol may induce memory facilitation through an increase of the release of acetylcholine in the brain. Post-training administration of a high dose of clenbuterol (1.0 mg/kg, ip) significantly impaired retention. Clenbuterol (1.0 mg/kg, ip)-induced impairment of retention was completely prevented by simultaneous post-training administration of oxotremorine (6.25, 12.5, or 50.0 micrograms/kg, ip). The centrally acting anticholinesterase physostigmine (21.5 or 68.0 micrograms/kg, ip) partially prevented clenbuterol-induced impairment of memory. The peripherally acting anticholinesterase neostigmine (68.0 micrograms/kg, ip) modified neither retention nor the amnestic effects of clenbuterol. Considered together, these findings are consistent with the view that brain muscarinic cholinergic mechanisms are involved in both the facilitatory and impairing effect of post-training clenbuterol on the modulation of memory storage.     

The effects of the dopamine D1 receptor antagonist SCH23390 on memory reconsolidation following reminder-activated retrieval in day-old chicks

This series of experiments examined the involvement of the dopamine D1 receptor antagonist, SCH23390, on memory reconsolidation following reminder-activated retrieval. Day-old male New HampshirexWhite Leghorn chicks were trained on a single trial passive avoidance task. A dose of 0.5 mg/kg of SCH23390 was administered subcutaneously 5 min before reminder trials, which were presented at 30, 60, and 90 min following training. Memory deficits were observed when reminder trials were presented at 30 and 60 min following training, but not when a reminder was presented at 90 min. No effect on memory retention was observed when reminder trials were not presented, suggesting that reconsolidation mechanisms were both contingent on the presentation of the reminder and independent of the consolidation process. Following a reminder presented at 60 min post-training, deficits in memory retention emerged between 45 and 60 min. The deficit was prolonged, lasting for up until 48 h after reminder presentation. The results indicate an important role for the D1 receptor in reconsolidation processes.     

Sound sequence discrimination learning motivated by reward requires dopaminergic D2 receptor activation in the rat auditory cortex

We have previously reported that sound sequence discrimination learning requires cholinergic inputs to the auditory cortex (AC) in rats. In that study, reward was used for motivating discrimination behavior in rats. Therefore, dopaminergic inputs mediating reward signals may have an important role in the learning. We tested the possibility in the present study. Rats were trained to discriminate sequences of two sound components, and licking behavior in response to one of the two sequences was rewarded with water. To identify the dopaminergic inputs responsible for the learning, dopaminergic afferents to the AC were lesioned with local injection of 6-hydroxydopamine (6-OHDA). The injection attenuated sound sequence discrimination learning, while it had no effect on discrimination between the sound components of the sequence stimuli. Local injection of 6-OHDA into the nucleus accumbens attenuated sound discrimination learning. However, not only discrimination learning of sound sequence but also that of the sound components were impaired. SCH23390 (0.2 mg/kg, i.p.), a D1 receptor antagonist, had no effect on sound sequence discrimination learning, while it attenuated the licking behavior to unfamiliar stimuli. Haloperidol (0.5 mg/kg, i.p.), a D2 family antagonist, attenuated sound sequence discrimination learning, while it had no clear suppressive effect on discrimination of two different sound components and licking. These results suggest that D2 family receptors activated by dopaminergic inputs to the AC are required for sound sequence discrimination learning.