Effects of four antipsychotics on punished responding in rats

Wiley, Jenny L.; Compton, Amelia D.; Porter, Joseph H.

doi:10.1016/0091-3057(93)90237-n

Cited by 39 publications

(17 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The highest risperidone dose of 1.0 mg/kg utilized in this study is, therefore, a high dose of this drug with regard to D 2 and 5HT 2 antagonism, two pharmacological properties likely relevant to therapeutic response. Finally, the antipsychotic dose ranges utilized in these experiments are also consistent with prior dosing strategies to investigate anxiolytic-like effects in rodent behavioral models (Moore et al, 1992;Wiley et al, 1993;Inoue et al, 1996). Rodent investigations examining clozapine anxiolytic-like effects utilized maximal clozapine doses of 5.0-10.0 mg/kg (Spealman and Katz, 1980; Moore et al, 1994;Inoue et al, 1996).…”

Section: Antipsychotic Administration and Dosingmentioning

confidence: 63%

Olanzapine and Clozapine Increase the GABAergic Neuroactive Steroid Allopregnanolone in Rodents

Marx

VanDoren

Duncan

et al. 2003

Neuropsychopharmacol

132

View full text Add to dashboard Cite

The neuroactive steroid allopregnanolone is a potent g-aminobutyric acid type A (GABA A ) receptor modulator with anxiolytic and anticonvulsant effects. Olanzapine and clozapine also have anxiolytic-like effects in behavioral models. We therefore postulated that olanzapine and clozapine would elevate allopregnanolone levels, but risperidone and haloperidol would have minimal effects. Male rats received intraperitoneal olanzapine (2.5-10.0 mg/kg), clozapine (5.0-20.0 mg/kg), risperidone (0.1-1.0 mg/kg), haloperidol (0.1-1.0 mg/ kg), or vehicle. Cerebral cortical allopregnanolone and peripheral progesterone and corticosterone levels were determined. Adrenalectomized animals were also examined. Both olanzapine and clozapine increased cerebral cortical allopregnanolone levels, but neither risperidone nor haloperidol had significant effects. Olanzapine and clozapine also increased serum progesterone and corticosterone levels. Adrenalectomy prevented olanzapine-and clozapine-induced elevations in allopregnanolone. Allopregnanolone induction may contribute to olanzapine and clozapine anxiolytic, antidepressant, and mood-stabilizing actions. Alterations in this neuroactive steroid may result in the modulation of GABAergic and dopaminergic neurotransmission, potentially contributing to antipsychotic efficacy.

show abstract

Section: Antipsychotic Administration and Dosingmentioning

confidence: 63%

Olanzapine and Clozapine Increase the GABAergic Neuroactive Steroid Allopregnanolone in Rodents

Marx

VanDoren

Duncan

et al. 2003

Neuropsychopharmacol

132

View full text Add to dashboard Cite

show abstract

“…Benzodiazepines, barbituates, clozapine, haloperidol (Geller and Seifter, 1960;Wiley et al, 1993;Millan and Brocco, 2003;Paterson and Hanania, 2010) Vogel punished drinking Water-deprived rats are given access to water. Drinking behaviour is 'punished' with electrical shocks.…”

Section: Ratsmentioning

confidence: 99%

The age of anxiety: role of animal models of anxiolytic action in drug discovery

Cryan¹,

Sweeney²

2011

British J Pharmacology

237

188

View full text Add to dashboard Cite

Anxiety disorders are common, serious and a growing health problem worldwide. However, the causative factors, aetiology and underlying mechanisms of anxiety disorders, as for most psychiatric disorders, remain relatively poorly understood. Animal models are an important aid in giving insight into the aetiology, neurobiology and, ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in humans coupled with the associated multifaceted and descriptive diagnostic criteria, creates challenges in both animal modelling and in clinical research. In this paper, we describe some of the more widely used approaches for assessing the anxiolytic activity of known and potential therapeutic agents. These include ethological, conflict-based, hyponeophagia, vocalization-based, physiological and cognitive-based paradigms. Developments in the characterization of translational models are also summarized, as are the challenges facing researchers in their drug discovery efforts in developing new anxiolytic drugs, not least the ever-shifting clinical conceptualization of anxiety disorders. In conclusion, to date, although animal models of anxiety have relatively good validity, anxiolytic drugs with novel mechanisms have been slow to emerge. It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change.

show abstract

“…Thus, an add-on anxiolytic effect of an APD might be desirable. Whereas classic APDs are generally ineffective in animal models of anxiety, some positive findings have been obtained with novel APDs, though only few studies are available.In classic operant conflict procedures, clozapine and olanzapine have shown anxiolytic-like activity with a mechanism of action different from benzodiazepines (Moore et al 1994;Wiley et al 1993; Nanry et al 1995), whereas risperidone and remoxipride are ineffective.Selective antagonists at 5-HT 2 and muscarinic receptors are ineffective as well (Moore et al 1994). Using Vogel's test (shock-induced suppression of drinking behavior), amperozide has anticonflict activity of similar magnitude to diazepam (Gustafsson and Christensson 1990a).…”

mentioning

confidence: 99%

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Arnt

Skarsfeldt

1998

Neuropsychopharmacology

681

443

View full text Add to dashboard Cite

The pharmacological properties of the novel antipsychotic drugs (APDs) risperidone, sertindole, olanzapine, quetiapine, ziprasidone, remoxipride, and amperozide are reviewed and compared with haloperidol and clozapine. Focus is made on their receptor profiles, their effects in animal models used for evaluation of antipsychotic activity, and extrapyramidal side effects (EPS). In addition, the contrasting actions of these compounds on animal modelsDuring the last decade there has been a dramatic increase in the efforts to develop novel antipsychotic drugs (APDs) with improved clinical efficacy and fewer or no extrapyramidal side effects (EPS) than the classical APDs such as haloperidol and fluphenazine. These efforts were undoubtedly inspired by the previous development of clozapine, which fulfilled these criteria to a large extent, although having other troublesome side From the Pharmacological Research, H. Lundbeck A/S, Ohiliavej 9, DK-2500, Copenhagen-Valby, Denmark.Address correspondence to: J0rn Arnt, Pharmacological Research, H. Lundbeck A/5, Ottiliavej 9, DK-2500 Copenhagen-Valby, Denmark.Received January 6, 1997; revised June 26, 1997; accepted July 7, 1997. effects (Baldessarini and Frankenburg 1991; Coward 1992;Wagstaff and Bryson 1995;Buchanan 1995; Ashby and Wang 1996).The novel APDs were assigned the popular term "atypical antipsychotic" drugs to differentiate them from the classic or "typical" APDs or neuroleptics. The most widely accepted definition of a neuroleptic is a compound that has antipsychotic activity and induces EPS with high frequency. The definition of "a typicality" was equivocal, however, because the term was often used for drugs before any clinical results were available. For example, the term was applied to a compound that induced little or no catalepsy in rats, and that was effective in another model believed to reflect antipsychotic activity, e.g., inhibition of O-amphetamine (AMPH)-induced hypermotility. A more precise definition is to base it solely on clinical evidence as a wide differentiation between the dosages used to control psychosis and those inducing EPS-or on other aspects of clinical superior-0893-133X/98/$19.00 PI! 50893-133X(97)00112-7 64 J. Arnt and T. Skarsfeldt ity over classic APDs, e.g., efficacy on negative symptoms of schizophrenia or in drug-resistant patients (for recent review, see Kinan and Lieberman 1996). However, because these very different characteristics are difficult to incorporate in a common definition, we suggest that the terminology "atypical" is best avoided. Indeed, as will be discussed, novel APDs show many individual differences.The suggested alternative terminology "novel APO" is also not precise, but it can be defined as a compound that has been shown to inhibit positive symptoms of schizophrenia and has either been recently launched or is in phase II/III clinical development. Their specific profiles can be described more precisely, e.g., EPS-free APO, etc. It is not anticipated that novel APDs will be marketed in the future, unless hav...

show abstract

Effects of four antipsychotics on punished responding in rats

Cited by 39 publications

References 16 publications

Olanzapine and Clozapine Increase the GABAergic Neuroactive Steroid Allopregnanolone in Rodents

Olanzapine and Clozapine Increase the GABAergic Neuroactive Steroid Allopregnanolone in Rodents

The age of anxiety: role of animal models of anxiolytic action in drug discovery

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Contact Info

Product

Resources

About