Effects of drugs on punished behavior: Pre-clinical test for anxiolytics

Pollard, Gerald T.; Howard, James L.

doi:10.1016/0163-7258(90)90075-d

Cited by 62 publications

(24 citation statements)

References 138 publications

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“…The OFT and VT have been well established as standard procedures sensitive to the anxiolytic-like effects of drugs (Pollard et al, 1990). In previous studies performed in our laboratory these two tests were found to be sensitive to the anxiolytic-like action of numerous compounds acting via a variety of neurotransmitter and receptor pathways (Stefafiski et al, 1992;P~a~nik et al, 1994;Jessa et al, 1996).…”

Section: Discussionmentioning

confidence: 98%

Benzodiazepine-GABAA receptor complex ligands in two models of anxiety

Nazar

Jessa

Płaźnik

1997

J. Neural Transmission

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In the present study, the actions of several compounds with different intrinsic activities and BDZ receptor selectivity were examined in two well established animal models of anxiety: the open field test (OFT) and Vogel's punished drinking text (VT). Full agonists at the BDZ GABAA receptor (midazolam and diazepam) showed anxiolytic-like effects in both tests; however, the doses necessary to disinhibit animal behavior controlled by fear were higher in the VT than in the OFT. None of the partial BDZ receptor agonists studied (bretazenil, Ro 19-8022 and abecarnil) diminished neophobia-like behavior of rats in the OFT, and their sedative influence on gross behavior prevailed. On the other hand, all three drugs produced a clear-cut anxiolytic effect in the VT. A selective BDZ, receptor subtype full agonist (zolpidem) had a similar profile of action to that of partial agonists with an even stronger sedative effect in the OFT. Alpidem (a selective BDZ1 receptor partial agonist) did not reveal any anxiolytic action in either test. Flumazenil (an antagonist at the BDZ-GABAA receptors) also produced no effect in the OFT, or the VT. An inverse BDZ receptor agonist, beta-carboline-3-carboxylate methyl ester (beta-CCM), evoked an anxiogenic-like response in the OFT, but not in the VT. In summary, it appeared that partial agonists and selective ligands at BDZ1 receptors revealed less advantageous anxiolytic-like action than did full allosteric GABAA receptor modulators. This study also indicates the test dependent profiles of action of BDZ-GABAA receptor ligands. It also indirectly suggests a different neurobiological background underlying the applied tests.

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Section: Discussionmentioning

confidence: 98%

Benzodiazepine-GABAA receptor complex ligands in two models of anxiety

Nazar

Jessa

Płaźnik

1997

J. Neural Transmission

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“…NPY produced potent anxiolytic-like behavioral e¤ects in the conßict test, an established animal model of anxiety with good predictive ability for clinically e¤ective anxiolytics (for review, see Pollard and Howard 1990). Low doses of NPY (4 and 6 µg, ICV) produced a dose-dependent increase in punished responding in the conßict test as reßected by increased lever pressing in the incremental shock period.…”

Section: Discussionmentioning

confidence: 98%

Anxiolytic activity of NPY receptor agonists in the conflict test

Britton¹,

Southerland²,

Uden³

et al. 1997

Psychopharmacology

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This investigation examined receptor subtype specificity and possible modulation by GABAa receptor ligands of NPY-induced behavioral responses to stressful stimuli. First, a series of NPY receptor agonists were examined for their potential effects on punished responding in a conflict test modified for incremental shock. NPY, peptide YY (PYY) and NPY Y1 receptor agonists [Leu31,Pro34]-NPY and [Gly6, Glu26,Lys26,Pro34]-NPY produced increases in punished responding in the conflict test. No significant effects on unpunished responding were noted. The pattern of responding was similar to that observed with the benzodiazepine agonist chlordiazepoxide. Neither pancreatic peptide (PP) nor the Y2 agonists NPY13-36 or [Glu2,32,Ala6,Dpr27,Lys28]-NPY significantly altered punished or unpunished responding. Of significance, the atypical Y1 agonist [Cys7,21,Pro34]-NPY produced negligible effects on punished responding, consistent with the presence of a subclass of Y1 receptors. Second, the anxiolytic effects of NPY were subjected to treatments that block actions at the GABAa receptor complex. The increase in punished responding produced by NPY was not altered by administration of the benzodiazepine antagonist flumazenil and only partially blocked by the picrotoxinin receptor ligand isopropylbicyclophosphate (10 and 15 microg/kg). These findings further support the hypothesis that the pharmacologic substrates for the anxiolytic-like actions of NPY may be mediated by the Y1 receptor subtype and suggest that these actions are independent of either the benzodiazepine or picrotoxinin binding sites of the GABA/benzodiazepine receptor complex.

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“…An increase in unpunished responses induced by a NMDAr antagonist has already been described by Wiley et al (1998) using the Geller-Seifter conflict paradigm. Benzodiazepine anxiolytic drugs have stimulant effects on feeding and drinking behavior (Bainbridge 1968;Cooper and Francis 1979), which is one of the main critics on anxiety tests that use food or water as rewards (Treit 1985;Pollard and Howard 1990). However, glutamatergic neurotransmission in the PAG has not been related to thirst mechanism.…”

Section: Discussionmentioning

confidence: 99%