Effects of LSD on classical conditioning as a function of CS-UCS interval: Relationship to reflex facilitation

Harvey, J.; Gormezano, I.; Cool-Hauser, V.A.; Schindler, Charles W.

doi:10.1016/0091-3057(88)90477-7

Cited by 29 publications

(16 citation statements)

References 27 publications

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“…We reported elsewhere that the magnitude of the NM reflex can be significantly enhanced by agonists at the 5-HT 2 receptor (Harvey et al 1988;Romano and Harvey 1994), while in the present study, several 5-HT 2 receptor antagonists were able significantly to decrease response magnitude. Our results are in general agreement with a number of studies that have suggested that serotonin may play an important role in the regulation of motor function (Jacobs and Fornal 1993;Wallis 1994) and that have identified the 5-HT 2 receptor as the mediator of these effects (McCall and Aghajanian 1980;Sugihara et al 1995).…”

Section: Role Of Serotonin In Motor Functioncontrasting

confidence: 67%

“…5-HT 1A receptor agonists had no effect or produced a slight retardation of learning (Alhaider et al 1993;Harvey 1996;Welsh et al 1998b). The enhancement of associative learning produced by 5-HT 2 agonists was found in varying situations to be accompanied by an increase in the amplitude of the unconditioned response (Schindler et al 1985;Harvey et al 1988;Romano et al 1991;Harvey 1993, 1994). More recently, we found that the 5-HT 2 antagonists ritanserin and MDL-11,939 produced a retardation of learning and a decrease in the amplitude of the unconditioned response, effects that were opposite to those of the 5-HT 2 agonists, while another 5-HT 2 antagonist, LY-53,857, had no effect on either measure (Welsh et al 1998a).…”

Section: Introductionmentioning

confidence: 95%

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Effect of 5-HT 2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism

et al. 1999

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This study examined the role of the serotonin 5-HT2 receptor in motor function by examining the effect of antagonists on the motor performance of a cranial nerve reflex, the nictitating membrane (NM) reflex of the rabbit. The NM reflex was elicited by varying intensities of a tactile stimulus and the magnitudes of the elicited responses were measured at each intensity. Dose-response curves were obtained for the effects of several 5-HT2 receptor antagonists on response magnitude. d-Bro-molysergic acid diethylamide (BOL), LY-53,857 and ketanserin had no significant effect on the magnitude of the NM reflex, indicating that they are neutral antagonists. However, the 5-HT2 receptor antagonists ritanserin, MDL-11,939 and mianserin produced a significant reduction in response magnitude with no significant effects on response frequency, suggesting that they were acting as inverse agonists at the 5-HT2 receptor. The reduction in reflex magnitude produced by mianserin (10 micromol/kg) was fully blocked by BOL (5.8 micromol/kg), supporting the conclusion that mianserin was producing a reduction in reflex magnitude through an effect at the 5-HT2 receptor. The occurrence of inverse agonism suggests the possible existence of constitutive activity in vivo. We conclude that the 5-HT2 receptor (either 2A or 2C) plays an important role in motor function, perhaps by providing a tonic influence on motor systems.

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Section: Role Of Serotonin In Motor Functioncontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 95%

Effect of 5-HT 2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism

et al. 1999

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“…LSD significantly enhanced CR acquisition at short (100 msec) and long (800 msec) CS-US intervals, but failed to do so at the optimum intervals of 200 and 400 msec ( Fig. 2A; Harvey et al 1988). This is further illustrated by acquisition curves in Figure 2, B, C, and D. At the 200-msec CS-US interval, both LSD-injected and vehicle control groups acquired CRs rapidly and at the same rate (Fig.…”

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

confidence: 99%

“…The 200-, 400-, and 800-msec CS-US intervals represent trace conditioning of 100, 300, and 500 msec, respectively. Data are taken from Harvey et al (1988). Figure 3 The relationship between the mean percentage of CRs generated by various NM conditioning procedures in control animals (abscissa) and the degree of enhancement of learning produced by LSD (13 µg/kg).…”

Section: Figurementioning

confidence: 99%

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Role of the Serotonin 5-HT_2A Receptor in Learning

Harvey¹

2003

Learn. Mem.

188

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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Use of classical conditioning procedures in behavioral pharmacology

Schindler

Harvey

1990

Drug Development Research

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While operant conditioning clearly dominates the field of behavioral pharmacology, over the past 10 years, classical conditioning has been used more frequently to study the effect of drugs on behavior. In particular, the rabbit nictitating membrane response (NMR) has been used to study the effects of drugs on learning. This procedure offers a number of advantages over other assessments of learning in mammals to the study of drug effects on learning. First, because the rabbit NMR is well characterized behaviorally, it is possible to relate a drug effect to a particular behavioral process (e.g., to an effect directly on learning vs. an effect on the psychological processing of the unconditioned stimulus). In addition, with recent advances in determining the neuroanatomical basis of the conditioned NMR, it may also be possible to relate a drug effect on learning to an effect at a particular anatomical locus. Finally, because the conditioned response is acquired rapidly, the effect of a drug on learning can be assessed rapidly within a large group of animals. The current paper details the behavioral techniques which have been developed to study the effects of drugs, in particular the opioids, on classical Conditioning. A number of studies which have used classical conditioning procedures in the rabbit to study drug effects on acquisition, maintenance, and differentiation of conditioned responses are reviewed.

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Effects of LSD on classical conditioning as a function of CS-UCS interval: Relationship to reflex facilitation

Cited by 29 publications

References 27 publications

Effect of 5-HT 2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism

Effect of 5-HT 2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism

Role of the Serotonin 5-HT_2A Receptor in Learning

Use of classical conditioning procedures in behavioral pharmacology

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Effects of LSD on classical conditioning as a function of CS-UCS interval: Relationship to reflex facilitation

Cited by 29 publications

References 27 publications

Effect of 5-HT 2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism

Effect of 5-HT 2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism

Role of the Serotonin 5-HT2A Receptor in Learning

Use of classical conditioning procedures in behavioral pharmacology

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Role of the Serotonin 5-HT_2A Receptor in Learning