Inactivation of the 5-HT(7) receptor partially blocks phencyclidine-induced disruption of prepulse inhibition.
Svetlana Semenova, Mark A. Geyer, J Gregor Sutcliffe, Athina Markou, Peter B Hedlund
Biological Psychiatry January 1, 2008 DOI: 10.1016/j.biopsych.2006.12.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Mice lacking the 5-HT7 receptor (5-HT7-/-) and wild-type (5-HT7+/+) mice |
| Interventions | Phencyclidine (PCP) SB-269970 Apomorphine Amphetamine |
| Dose | PCP 10 mg/kg; apomorphine 5 mg/kg; amphetamine 7.5 mg/kg |
| Topics | Serotonin |
| Key findings | PCP-induced disruption of prepulse inhibition was reduced in 5-HT7 receptor knockout mice compared with wild-type mice, but the 5-HT7 antagonist SB-269970 did not alter PCP-disrupted PPI. Apomorphine- and amphetamine-induced PPI disruption was comparable across genotypes. The authors conclude that the 5-HT7 receptor plays a partial role in the glutamatergic PPI model and no role in the dopaminergic PPI model. |
Abstract
Studies have implicated the serotonin (5-HT)(7) receptor in physiological and pathophysiological phenomena, including thermoregulation, central control of micturition and locomotion, regulation of circadian rhythm, sleep, and depression. Further, several antidepressant and antipsychotic drugs have high affinity for the 5-HT(7) receptor. We examined the role of 5-HT(7) receptors in a rodent analogue of sensorimotor gating deficits in schizophrenia: phencyclidine (PCP)-induced disruption of prepulse inhibition (PPI) of acoustic startle. We used mice lacking the 5-HT(7) receptor due to a targeted inactivation of this receptor gene and the selective 5-HT(7) receptor antagonist SB-269970. SB-269970 did not affect either baseline PPI or PCP-disrupted PPI. There was no difference between 5-HT(7)(+/+) and 5-HT(7)(-/-) mice in startle reactivity or PPI regardless of prepulse intensity (74-82 dB), interstimulus interval (25-500 msec), or pulse intensity (90-120 dB). Nevertheless, disruption of PPI produced by PCP (10 mg/kg) in wild-type mice was reduced in 5-HT(7)(-/-) mice, although it was not affected by the 5-HT(7) antagonist SB-269970. By contrast, the PPI-disruptive effects of apomorphine (5 mg/kg) and amphetamine (7.5 mg/kg) were comparable in both genotypes. The results indicate a partial role for the 5-HT(7) receptor in the glutamatergic PPI model of sensorimotor gating deficits in schizophrenia that is sensitive to atypical antipsychotics and no involvement of this receptor in the dopaminergic PPI model that is sensitive to typical antipsychotics. Thus, the 5-HT(7)(-/-) mice may provide a useful tool to study the role of 5-HT(7) receptor in the action of atypical antipsychotic drugs and schizophrenia.
Comparable studies
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| 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
- The role of 5-hydroxytryptamine 7 receptors in the phencyclidine-induced novel object recognition deficit in rats. Journal of Pharmacology and Experimental Therapeutics August 2011
- The role of serotonin in the NMDA receptor antagonist models of psychosis and cognitive impairment. Psychopharmacology February 1, 2011