Can the DRL 72s schedule selectively reveal antidepressant drug activity?

Psychopharmacology (Berl)

Neurobiology Division, Fondax, Puteaux, France.

Published: January 1995

The effects of three antidepressants, desipramine (2.5-20 mg/kg) tranylcypromine (0.63-2.5 mg/kg) mianserin (1.25-10 mg/kg) and three non-antidepressants, chlordiazepoxide (CDP; 1.25-10 mg/kg) haloperidol (0.02-0.16 mg/kg) d-amphetamine (0.31-1.25 mg/kg) were evaluated in rats responding for water reinforcement under a DRL 72s schedule. The antidepressants all produced dose-related decreases in overall response rates, but no significant changes in reinforcement frequency. In contrast, the anxiolytic CDP did increase the number of reinforcers obtained. Haloperidol decreased both reinforcers and responses whilst d-amphetamine stimulated responding, thereby decreasing reinforcement frequency. An analysis of the modes of inter-response times (IRTs) revealed no significant shifts in the peaks of the IRT distributions for most of the drugs tested. Amphetamine, however, (0.31 and 0.63 mg/kg) decreased the modal values in correspondence with the shift to the left of the peak of responding caused by this compound. These results are discussed in the context of the use of the DRL 72s procedure as a screening test for antidepressant drugs.

Download full-text PDF

Source
http://dx.doi.org/10.1007/BF02245181DOI Listing

Publication Analysis

Top Keywords

drl 72s
12
72s schedule
8
125-10 mg/kg
8
reinforcement frequency
8
mg/kg
7
schedule selectively
4
selectively reveal
4
reveal antidepressant
4
antidepressant drug
4
drug activity?
4

Similar Publications

Background: In clinical studies, psychedelics including psilocybin and D-lysergic acid diethylamide (LSD) demonstrate rapid and persistent antidepressant effects. Since the effective treatment with psychedelics is usually provided with psychotherapy, it is debatable whether their prolonged efficacy can be observed in infrahuman species. Preclinical reports on psychedelics' effects most often address their acute actions, and different tests and models provide inconsistent results.

View Article and Find Full Text PDF
Article Synopsis
  • (S)-ketamine has shown rapid antidepressant effects that differ from (R)-ketamine, which has yet to be thoroughly studied, despite resulting in fewer dissociative symptoms.
  • Research indicates that (S)-ketamine causes time underestimation in the perception of time, while (R)-ketamine has no effect on timing, suggesting a unique mechanism for each.
  • Both (S)-ketamine and fluoxetine increased performance-related metrics in a task with rats, but fluoxetine uniquely reduced impulsivity, raising questions about the role of opioid receptors and the influence of naloxone on these medications' effectiveness.
View Article and Find Full Text PDF

Layer V pyramidal neurons constitute principle output neurons of the medial prefrontal cortex (mPFC)/neocortex to subcortical regions including the intralaminar/midline thalamic nuclei, amygdala, basal ganglia, brainstem nuclei and the spinal cord. The effects of 5-hydroxytryptamine (5-HT) on layer V pyramidal cells primarily reflect a range of excitatory influences through 5-HT receptors and inhibitory influences through non-5-HT receptors, including 5-HT receptors. While the 5-HT receptor is primarily a postsynaptic receptor on throughout the apical dendritic field of 5-HT receptors, activation of a minority of 5-HT receptors also appears to increase spontaneous excitatory postsynaptic currents/potentials (EPSCs/EPSPs) via a presynaptic effect on thalamocortical terminals arising from the midline and intralaminar thalamic nuclei.

View Article and Find Full Text PDF

Both an agonist and its associated prodrug for metabotropic glutamate (mGlu) receptors demonstrated anxiolytic efficacy in large, randomized, multicenter, double-blind, placebo-controlled trials studying patients with generalized anxiety disorder (GAD). These mGlu receptor agonists produced robust preclinical anxiolytic-like effects in rodent models. Several different metabotropic glutamate receptor positive allosteric modulators have been found to produce antidepressant-like effects on several preclinical screening paradigms, including differential-reinforcement-of-low-rate 72-second (DRL 72-s) behavior [increased reinforcers, decreased response rate, and cohesive rightward shifts in inter-response time distributions].

View Article and Find Full Text PDF

Interactions of Hallucinogens with the Glutamatergic System: Permissive Network Effects Mediated Through Cortical Layer V Pyramidal Neurons.

Curr Top Behav Neurosci

September 2018

Global Medical Science, CNS and Pain, Astellas Pharma Global Development, 1 Astellas Way, Northbrook, IL, 60062, USA.

Recordings made from layer V (L5) pyramidal cells of the prefrontal cortex (PFC) and neocortex in rodent slice preparations have shown that serotonin (5-hydroxytryptamine, 5-HT) and serotonergic hallucinogens induce an increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in the apical dendritic field by activating 5-HT receptors. Serotonergic hallucinogens induce late EPSCs and increase recurrent network activity when subcortical or mid-cortical regions are stimulated at low frequencies (e.g.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!