Hippocampal serotonin depletion unmasks differences in the hyperlocomotor effects of phencyclidine and MK-801: quantitative versus qualitative analyses
Wendy K. Adams, Adam L. Halberstadt, Maarten Van den Buuse
Frontiers in Pharmacology 2013 DOI: 10.3389/fphar.2013.00109 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Qualitative Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Phencyclidine (PCP) MK-801 5 7-dihydroxytryptamine (5 |
| Dose | PCP 0.5, 2.5 mg/kg; MK-801 0.1 mg/kg |
| Measures | spatial d, entropy |
| Topics | Serotonin |
| Keywords | Phencyclidine Dorsal raphe nucleus Nmda receptor Hippocampus Raphe nuclei Hippocampal formation Endocrinology Median raphe nucleus Dizocilpine |
| Citations | 11 |
| Key findings | Serotonergic lesions of the dorsal hippocampus potentiate PCP-induced hyperlocomotion but not that of MK-801, revealing a functional differentiation between the two NMDA receptor antagonists. |
Abstract
Antagonism of N-methyl-D-aspartate (NMDA) receptors by phencyclidine (PCP) is thought to underlie its ability to induce a schizophrenia-like syndrome in humans, yet evidence indicates it has a broader pharmacological profile. Our previous lesion studies highlighted a role for serotonergic projections from the median, but not dorsal, raphe nucleus in mediating the hyperlocomotor effects of PCP, without changing the action of the more selective NMDA receptor antagonist, MK-801. Here we compared locomotor responses to PCP and MK-801 in rats that were administered 5,7-dihydroxytryptamine (5,7-DHT) into either the dorsal or ventral hippocampus, which are preferentially innervated by median and dorsal raphe, respectively. Dorsal hippocampus lesions potentiated PCP-induced hyperlocomotion (0.5, 2.5 mg/kg), but not the effect of MK-801 (0.1 mg/kg). Ventral hippocampus lesions did not alter the hyperlocomotion elicited by either compound. Given that PCP and MK-801 may induce different spatiotemporal patterns of locomotor behavior, together with the known role of the dorsal hippocampus in spatial processing, we also assessed whether the 5,7-DHT-lesions caused any qualitative differences in locomotor responses. Treatment with PCP or MK-801 increased the smoothness of the path traveled (reduced spatial d) and decreased the predictability of locomotor patterns within the chambers (increased entropy). 5,7-DHT-lesions of the dorsal hippocampus did not alter the effects of PCP on spatial d or entropy - despite potentiating total distance moved - but caused a slight reduction in levels of MK-801-induced entropy. Taken together, serotonergic lesions targeting the dorsal hippocampus unmask a functional differentiation of the hyperlocomotor effects of PCP and MK-801. These findings have implications for studies utilizing NMDA receptor antagonists in modeling glutamatergic dysfunction in schizophrenia.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 2
- Temporal dissociation of phencyclidine: Induced locomotor and social alterations in rats using an automated homecage monitoring system - implications for the 3Rs and preclinical drug discovery. Journal of Psychopharmacology July 1, 2020
- The novel ketamine analog methoxetamine produces dissociative-like behavioral effects in rodents. Psychopharmacology April 1, 2016
Cites 11
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- Study of a New Schizophrenomimetic Drug—Sernyl Archives of Neurology And Psychiatry March 1, 1959
- The role of serotonin in the NMDA receptor antagonist models of psychosis and cognitive impairment. Psychopharmacology February 1, 2011
- 5-HT_2A and 5-HT_2C Receptors Exert Opposing Effects on Locomotor Activity in Mice Neuropsychopharmacology July 1, 2009
and 6 more in the library