Effects of LSD, Ritanserin, 8-OH-DPAT, and Lisuride on Classical Conditioning in the Rabbit

Welsh, Sarah E

doi:10.1016/s0091-3057(97)00436-x

Cited by 34 publications

(22 citation statements)

References 29 publications

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“…The results of this study indicate that the 5-HT 2A receptor plays an important role in the cortical circuitry involved in the formation of associations, and are consistent with the fact that agonists at the 5-HT 2A receptor such as LSD (Marek and Aghajanian 1996) produce a robust enhancement of associative learning (Harvey 1996;Welsh et al 1998). A number of other studies have also indicated an important role for the 5-HT 2A receptor in cognitive function.…”

Section: Role Of 5-ht 2a Receptors In Cognitive Processessupporting

confidence: 87%

“…Drugs acting as agonists at the 5-HT 2A receptor have been demonstrated to enhance associative learning during acquisition of the rabbit's classically conditioned eyeblink response (Romano et al 1991;Harvey 1996Harvey , 2003Welsh et al 1998), and working memory in the primate (Williams et al 2002). The serotonin 5-HT 2A receptor has also been demonstrated to mediate the hallucinatory actions of drugs such as LSD (d-lysergic acid diethylamide) (Marek and Aghajanian 1996), and to play an important role in the therapeutic effects of antipsychotic drugs (Arora and Meltzer 1991).…”

Section: Introductionmentioning

confidence: 99%

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Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

et al. 2004

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Section: Role Of 5-ht 2a Receptors In Cognitive Processessupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

et al. 2004

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“…However, it is not clear whether the enhancement of learning produced by 5-HT 2A agonists in our studies might not also be produced by agonists acting at other serotonin receptor subtypes. So far, only the 5-HT 1A receptor agonists 8-OH-DPAT and lisuride have been examined, and they had no effect on acquisition of the eyeblink response (see Table 1; Welsh et al 1998a). However, investigators using other measures of learning have reported that 5-HT 1A receptor agonists impair learning.…”

Section: Serotonin 5-ht 2a Receptor Agonists Enhance Associative Learmentioning

confidence: 99%

“…Acquisition of the NM response was measured during the pairing of a tone CS and air puff US. Data are taken from Welsh et al (1998a).…”

Section: Figurementioning

confidence: 99%

Role of the Serotonin 5-HT_2A Receptor in Learning

Harvey¹

2003

Learn. Mem.

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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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“…Studies employing classical conditioning of the rabbit's nictitating membrane (NM) response or the conditioned avoidance response (CAR) in the rat have demonstrated that agonists at the serotonin 5-HT 2A/2C receptor uniformly enhance learning (Gimpl et al 1979;Harvey et al 1982;Siegel and Freedman 1988;Romano et al 1991;Alhaider et al 1993;Romano and Harvey 1994), while agonists at the 5-HT 1A receptor have no effect (Alhaider et al 1993;Welsh et al 1997). In contrast, a survey of studies employing varying behavioral procedures and species, but in which drug effects on learning were measured explicitly as changes in performance as a function of conditioning trials, indicated that antagonists at the 5-HT 2A/2C receptor have mixed effects on learning (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Effects of serotonin 5-HT 2A/2C antagonists on associative learning in the rabbit

1998

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The 5-HT(2A/2C) receptor antagonist, ritanserin, was reported to retard the acquisition of conditioned responses (CRs) during classical conditioning of the rabbit's nictitating membrane (NM) response. The present study compared the effects of ritanserin on acquisition of CRs to a tone conditioned stimulus (CS) with that of the 5-HT(2A/2C) receptor antagonist, LY-53,857 and the 5-HT2A selective antagonist, MDL-11,939. All three drugs were injected at equimolar doses of 0.067, 0.67 and 6.7 micromol/kg, SC, 1 h before behavioral testing. Ritanserin and MDL-11,939 retarded CR acquisition to a tone CS, while LY-53,857 had no effect. Control experiments demonstrated that ritanserin (1 micromol/kg), MDL-11,939 (1 micromol/kg) and LY-53,857 (2 micromol/kg) had no effect on baseline responding or non-associative responding to the CS. However, both ritanserin and MDL-11,939 impaired the performance of the unconditioned NM reflex, as measured by a decrease in UR amplitudes on US alone trials, while LY-53,857 had no effect. In previously trained animals, ritanserin robustly impaired the performance of CRs, as measured by a reduced ability of the CS to elicit CRs, while the effects of LY-53,857 and MDL-11,939 were marginal. The retardation of associative learning produced by ritanserin and MDL-11,939 may have been due, at least in part, to their impairment of the NM reflex arc. Since MDL-11,939 is a highly selective 5-HT2A antagonist, the retardation of learning and impairment of UR amplitudes produced by MDL-11,939 and ritanserin may have been due to blockade of the 5-HT2A receptor. The ability of ritanserin and MDL-11,939 to produce effects on learning and performance that were opposite to that of 5-HT(2A/2C) agonists suggests that they may be acting as inverse agonists at that receptor. These results stress the importance of the serotonergic system for optimal associative learning and motor function.

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Effects of LSD, Ritanserin, 8-OH-DPAT, and Lisuride on Classical Conditioning in the Rabbit

Cited by 34 publications

References 29 publications

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

Role of the Serotonin 5-HT_2A Receptor in Learning

Effects of serotonin 5-HT 2A/2C antagonists on associative learning in the rabbit

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Effects of LSD, Ritanserin, 8-OH-DPAT, and Lisuride on Classical Conditioning in the Rabbit

Cited by 34 publications

References 29 publications

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

Role of the Serotonin 5-HT2A Receptor in Learning

Effects of serotonin 5-HT 2A/2C antagonists on associative learning in the rabbit

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Product

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Role of the Serotonin 5-HT_2A Receptor in Learning