A unique enhancement of associative learning produced by methylenedioxyamphetamine

Ag, Romano; Nm, Bormann; Ja, Harvey

doi:10.1097/00008877-199106000-00006

Cited by 34 publications

(22 citation statements)

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“…The conditioning apparatus including the computer hardware and ASYST software for stimulus control and data acquisition has been described in detail elsewhere (Romano et al, 1991). Movements of the right nictitating membrane (NM) were measured by a potentiometer and digitized every 5 msec with a resolution of 0.03 mm of NM movement per analog-to-digital count.…”

Section: Methodsmentioning

confidence: 99%

The p38 Mitogen-Activated Protein Kinase Is Involved in Associative Learning in Rabbits

Zhen

Romano

et al. 2001

J. Neurosci.

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This study examined the role of the mitogen-activated protein kinase (MAPK) family during acquisition of the rabbit's classically conditioned eye-blink response. Eye-blink conditioning produced a significant, bilateral activation of both extracellular signal-regulated protein kinases (ERKs) and p38 MAPK in the anterior cerebellar vermis. There was also a significant bilateral activation of ERKs in the dorsal hippocampus with no change in p38 MAPK. These changes were seen at 2 min after the last conditioning session, were maintained for at least 180 min, and occurred without any change in the protein expression of either ERKs or p38 MAPK. There were no changes in ERKs or p38 MAPK in frontal cortex, in cerebellar hemispheral lobule VI, or in a section of brainstem containing the inferior olive. Moreover, the stress-related protein kinase Jun N-terminal kinase (JNK), another subfamily of MAPKs, was not altered in any of the brain regions examined. Animals receiving explicitly unpaired presentations of a conditioned stimulus and an unconditioned stimulus did not acquire conditioned responses (CRs) and did not demonstrate any changes in ERKs, p38 MAPK, or JNK. The intraventricular injection of SB203580, a selective p38 MAPK inhibitor, significantly retarded CR acquisition and blocked the learning-related increases in p38 MAPK activity in the anterior vermis. PD98059, a selective MAPK kinase inhibitor, had a smaller and only marginally significant effect on CR acquisition, although it did block the learning-related increases in ERK activity in both the hippocampus and anterior vermis. These results indicate that p38 MAPK is activated during associative learning and may play a role in the transcriptional events that lead to memory consolidation.

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Section: Methodsmentioning

confidence: 99%

The p38 Mitogen-Activated Protein Kinase Is Involved in Associative Learning in Rabbits

Zhen

Romano

et al. 2001

J. Neurosci.

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“…The apparatus has been described in detail (Romano, Bormann & Harvey, 1991 (Gormezano, 1966) The animals were subjected to a 3-phase procedure in the 10 days that followed the surgery: light conditioning ( (Welsh & Harvey, 1989c). Three minutes after either an injection that impaired CRs or a fourth non-effective injection, 7 ,u of lidocaine was continuously infused into the cerebellum at the rate of 01 jl min-'.…”

Section: Methodsmentioning

confidence: 99%

Pavlovian conditioning in the rabbit during inactivation of the interpositus nucleus.

Welsh

Harvey

1991

The Journal of Physiology

135

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SUMMARY1. We have examined the role of the anterior interpositus nucleus (AIP) of the cerebellum in Pavlovian conditioning of the nictitating membrane response (NMR) of the rabbit with the use of reversible brain lesions produced by the local anaesthetic lidocaine. Previous experiments have demonstrated that destructive lesions of the AIP prevent the performance of conditioned NMRs (CRs). Microinjections of lidocaine into the AIP were used in the present experiment to determine whether the deficit in the performance of CRs resulted from a deficit in learning or memory.2. A 3-phase procedure was employed to determine whether associative learning required the function of the AIP. In phase 1, rabbits were trained to make CRs to a flashing-light conditioned stimulus (CS) that was paired with an air-puff unconditioned stimulus (UCS) directed at the cornea. In phase 2, the AIP was anaesthetized during a session of conditioning in which a tone CS was paired with the UCS. Presentations of the light CS were interpolated throughout the tone conditioning in order to monitor the degree to which CRs were impaired by lidocaine. Phase 3 occurred after the effects of the lidocaine had dissipated and consisted of a test of retention to determine whether learning occurred during phase 2 but could not be expressed because of a performance deficit resulting from the inactivation of the AIP.3. Infusion of lidocaine into the AIP abolished CRs to the light CS and prevented the performance of CRs to the tone CS in phase 2. The effect of the infusion was specifically due to a conduction block of neurons and/or fibres in the lateral aspect of the AIP. The infusion of lidocaine into regions surrounding the AIP did not affect CRs elicited by the light CS or prevent acquisition of CRs to the tone. Infusions of saline directly into the AIP did not impair the performance of CRs to either the tone or light CS. Quantitative analysis of diffusion revealed that the abolition of CRs was accompanied by anaesthetization of the AIP.4. The retention test in phase 3 indicated that learning occurred normally during phase 2 when the AIP was inactivated and performance was abolished. When the function of the AIP was restored and performance had recovered, the subjects demonstrated a frequency of CRs to the tone CS that was indistinguishable from control subjects whose performance had never been impaired. MS 8897 J. P. WELSH AND J. A. HARVEY 5. The CRs observed during the retention test provided an unequivocal measure of associative learning. Control subjects that received explicitly unpaired presentations of the tone and air puff during the infusion of lidocaine responded at baseline levels to the tone when the function of the AIP was restored.6. We conclude that the AIP is not essential for Pavlovian conditioning of the NMR because learning occurs normally when the AIP is inactivated. Therefore, the AIP can neither be a site where memories for Pavlovian conditioning are stored nor a site that is essential for sensory processing which leads to associat...

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“…Control experiments using the explicitly unpaired presentations of CS and US indicated that the enhancement of CR acquisition produced by LSD, DOM, MDA, and MDMA was due to an enhancement of associative learning (Harvey et al 1982;Romano et al 1991;Romano and Harvey 1994). For example, baseline responding in control animals was low (1%-3%), as was responding to the unpaired tone stimulus (2%-8%).…”

Section: Learning and Memory 357mentioning

confidence: 99%

Role of the Serotonin 5-HT_2AReceptor in Learning

Harvey¹

2003

Learn. Mem.

189

148

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This study reviews the role of the serotonin 5-HT 2A receptor in learning as measured by the acquisition of the rabbit's classically conditioning nictitating membrane response, a component of the eyeblink response. Agonists at the 5-HT 2A receptor including LSD (d-lysergic acid diethylamide) enhanced associative learning at doses that produce cognitive effects in humans. Some antagonists such as BOL (d-bromolysergic acid diethylamide), LY53,857, and ketanserin acted as neutral antagonists in that they had no effect on learning, whereas others (MDL11,939, ritanserin, and mianserin) acted as inverse agonists in that they retarded learning through an action at the 5-HT 2A receptor. These results were placed in the context of what is known concerning the anatomical distribution and electrophysiological effects of 5-HT 2A receptor activation in frontal cortex and hippocampus, as well as the role of cortical 5-HT 2A receptors in schizophrenia. It was concluded that the 5-HT 2A receptor demonstrates constitutive activity, and that variations in this activity can produce profound alterations in cognitive states.The past few decades have brought an increasing awareness of serotonin's role in behavior. The development of drugs acting on the serotonergic system of brain that allow for the treatment of depression, anxiety, appetite regulation, and post-traumatic stress disorders has focused a great deal of attention on the role of serotonin in processes involving emotional states. Commensurate with our increasing understanding of the role of serotonin in behavioral processes has been the identification of at least seven serotonin (5-hydroxytryptamine; 5-HT) receptor sub-types. More recently, investigators have focused on the role of serotonin in cognitive functions, including learning and memory (Harvey 1996;Barnes and Sharp 1999;Meneses 1999Meneses , 2002Williams et al. 2002) and in the deficits in attention and associative processes seen in schizophrenia (Meltzer 1999). Serotonin receptor subtypes that have been demonstrated to occur in brain regions capable of playing a role in learning and memory include the 5-HT 1 , 5-HT 2 , 5-HT 3 , 5-HT 4 , 5-HT 6 , and 5-HT 7 class of receptors (Barnes and Sharp 1999;Meneses 2002). Table 1 summarizes studies that have examined the effects of serotonin agonists on learning. It can be seen that agonists at the 5-HT 1A receptor subtype had either no effect (n = 2) or impaired learning (n = 3), whereas both 5-HT 2A/2C and 5-HT 4 receptor agonists primarily improved learning. The majority of serotonin antagonists are reported to have no effect on learning (Table 2). Thus, all of the 5-HT 1A (n = 4) and 5-HT 3 (n = 4) antagonists that have been examined were found to have no effect on learning. However, two of the six 5-HT 2A/2C antagonists impaired learning, as did one of the two 5-HT 4 antagonists.Although the data cited above indicate that activation of serotonin receptors or their blockade can produce alterations in learning, these data do not provide the consistent outcomes that woul...

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A unique enhancement of associative learning produced by methylenedioxyamphetamine

Cited by 34 publications

References 0 publications

The p38 Mitogen-Activated Protein Kinase Is Involved in Associative Learning in Rabbits

The p38 Mitogen-Activated Protein Kinase Is Involved in Associative Learning in Rabbits

Pavlovian conditioning in the rabbit during inactivation of the interpositus nucleus.

Role of the Serotonin 5-HT_2AReceptor in Learning

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A unique enhancement of associative learning produced by methylenedioxyamphetamine

Cited by 34 publications

References 0 publications

The p38 Mitogen-Activated Protein Kinase Is Involved in Associative Learning in Rabbits

The p38 Mitogen-Activated Protein Kinase Is Involved in Associative Learning in Rabbits

Pavlovian conditioning in the rabbit during inactivation of the interpositus nucleus.

Role of the Serotonin 5-HT2AReceptor in Learning

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Role of the Serotonin 5-HT_2AReceptor in Learning