Use of classical conditioning procedures in behavioral pharmacology

Schindler, Charles W.; Harvey, J.

doi:10.1002/ddr.430200205

Cited by 13 publications

(4 citation statements)

References 76 publications

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“…The pattern of results obtained with harmaline on CR acquisition in this study was identical with that obtained previously with a number of other drugs (Harvey, 1987;Schindler and Harvey, 1990). Thus, a wide variety of drugs block associative learning by decreasing the excitatory properties of the CS (e.g., haloperidol, scopolamine, morphine) or increase associative learning by increasing the excitatory properties of the CS (e.g., d-lysergic acid diethylamide).…”

Section: Discussionsupporting

confidence: 90%

Harmaline-induced impairment of Pavlovian conditioning in the rabbit

Harvey¹,

Romano²

1993

J. Neurosci.

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In this study we examined the effects of harmaline on Pavlovian conditioning of the rabbit's nictitating membrane response. The acquisition of conditioned responses was determined during a single session consisting of 120 pairings of a tone-conditioned stimulus with a corneal air puff unconditioned stimulus. Harmaline severely retarded (5 mg/kg) or completely blocked (10 and 20 mg/kg) acquisition of conditioned responses. The blocked or retarded acquisition of conditioned responses could still be detected when the rabbits were tested 2 d after cessation of drug injections, suggesting that harmaline was affecting acquisition and not the motoric expression of conditioned responses. Control experiments established that harmaline (5 mg/kg) did not affect (1) baseline levels of responding, (2) the level of non-associative responding to the conditioned stimulus, (3) the amplitude or any of the temporal characteristics of the unconditioned response, (4) the development of habituation to the unconditioned stimulus, and (5) the threshold of the unconditioned stimulus for eliciting the unconditioned response. However, harmaline did produce a 12 dB increase in the intensity threshold of the conditioned stimulus for eliciting conditioned responses. We concluded that the primary effect of harmaline was to impair stimulus processing within brainstem circuits such as to reduce the excitatory properties of the conditioned stimulus, thus retarding its entry into associative learning. The results were discussed with respect to the possible role of the inferior olive in associative learning.

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Section: Discussionsupporting

confidence: 90%

Harmaline-induced impairment of Pavlovian conditioning in the rabbit

Harvey¹,

Romano²

1993

J. Neurosci.

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“…Secondly, they may alter the sensory properties of the CS and US, which would in turn affect learning and performance of CRs. Thirdly, they may impair learning-related plasticity (Schindler & Harvey, 1990). We consider our results in the context of these possibilities.…”

Section: Discussionmentioning

confidence: 89%

Reversible inactivations of the cerebellum prevent the extinction of conditioned nictitating membrane responses in rabbits.

Ramnani

Yeo

1996

The Journal of Physiology

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1. Studies show that reversible inactivation of the anterior interpositus nucleus (AIP) of the cerebellum with muscimol (a GABAA agonist) prevents acquisition of the classically conditioned nictitating membrane response (NMR) in the rabbit. Here, we have used reversible inactivations of the AIP with muscimol to investigate the role of the cerebellum in the extinction of this response. 2. Experimental subjects were implanted with cannulae targeted to the AIP, through which muscimol could be infused via an injector cannula. This experiment was divided into three phases lasting 4 days, separated by 3 day intervals. Experimental and unoperated control subjects received acquisition training in phase 1; in phases 2 and 3 they received extinction training. 3. Presentation of the conditioned stimulus (CS) alone in phase 2 produced normal extinction in control subjects. Muscimol inactivation of the AIP in experimental subjects during phase 2 prevented extinction of conditioned responses (CRs), shown by initial high CR frequency in the first post‐drug session of phase 3, which then extinguished in a manner indistinguishable from controls in phase 2. 4. Our findings support the suggestion that similar cerebellar circuitry is engaged in acquisition and extinction of NMR conditioning.

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“…Consequently, it has been used widely to model a variety of clinical states characterized by deficits in associative processes, including schizophrenia (Sears et al 2000), Alzheimer's dementia (Woodruff-Pak 2001), autism, and obsessive-compulsive disorder (Steinmetz et al 2001). Eyeblink conditioning has also provided an excellent model for examining the neuronal circuitry underlying associative learning (e.g., Thompson 1986;Harvey and Welsh 1996;Steinmetz 2000), the receptor systems that play a major role in the acquisition and retention of associative learning (e.g., Harvey 1987Harvey , 1996Schindler and Harvey 1990;Romano and Harvey 1992), and the molecular cascade that is responsible for the alterations in synaptic efficacy that are required for the permanent storage of learned associations (Geinisman et al 2001;Zhen et al 2001). The wide use of this behavioral paradigm is also due to the fact that alterations in the acquisition of conditioned responses (CRs) can be further analyzed in terms of alterations in nonassociative processes such as sensitization and pseudoconditioning, as well as alterations in performance factors.…”

Section: Classical Conditioning Of the Rabbit's Nictitating Membrane mentioning

confidence: 99%

Role of the Serotonin 5-HT_2A Receptor in Learning

Harvey¹

2003

Learn. Mem.

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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

Cited by 13 publications

References 76 publications

Harmaline-induced impairment of Pavlovian conditioning in the rabbit

Harmaline-induced impairment of Pavlovian conditioning in the rabbit

Reversible inactivations of the cerebellum prevent the extinction of conditioned nictitating membrane responses in rabbits.

Role of the Serotonin 5-HT_2A Receptor in Learning

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Use of classical conditioning procedures in behavioral pharmacology

Cited by 13 publications

References 76 publications

Harmaline-induced impairment of Pavlovian conditioning in the rabbit

Harmaline-induced impairment of Pavlovian conditioning in the rabbit

Reversible inactivations of the cerebellum prevent the extinction of conditioned nictitating membrane responses in rabbits.

Role of the Serotonin 5-HT2A Receptor in Learning

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Role of the Serotonin 5-HT_2A Receptor in Learning