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/BF02245181 | DOI Listing |
J Psychopharmacol
November 2023
Department of Behavioral Neuroscience and Drug Development, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
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 PDFEur Neuropsychopharmacol
February 2023
Behavioral Neuroscience and Drug Development, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland. Electronic address:
Prog Brain Res
October 2021
Consultant, Ardmore, PA, United States.
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 PDFJ Pharmacol Exp Ther
July 2020
Yale School of Medicine Department of Psychiatry, Ribicoff Research Facilities of the Connecticut Mental Health Center, New Haven, Connecticut.
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 PDFCurr 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 PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!