CB1 receptor stimulation in specific brain areas differently modulate anxiety-related behaviour.
Tiziana Rubino, Cinzia Guidali, Daniela Viganò, Natalia Realini, M Valenti, P Massi, Daniela Parolaro
Neuropharmacology January 2008 DOI: 10.1016/j.neuropharm.2007.06.024 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | THC |
| Dose | 10 micrograms (prefrontal cortex), 5 micrograms (ventral hippocampus), 1 microgram (basolateral amygdala) |
| Measures | elevated plus-maze |
| Topics | Anxiety |
| Key findings | Low-dose THC microinjected into the rat prefrontal cortex (10 micrograms) and ventral hippocampus (5 micrograms) produced anxiolytic-like effects in the elevated plus-maze, while higher doses lost this effect or appeared anxiogenic. In contrast, a low dose in the basolateral amygdala (1 microgram) produced an anxiogenic-like response, with higher doses ineffective. The authors report these effects were CB1-dependent and paralleled by increases (cortex, hippocampus) or decreases (amygdala) in CREB activation. |
Abstract
There is a general consensus that the effects of cannabinoid agonists on anxiety seem to be biphasic, with low doses being anxiolytic and high doses ineffective or possibly anxiogenic. Besides the behavioural effects of cannabinoids on anxiety, very few papers have dealt with the neuroanatomical sites of these effects. We investigated the effect on rat anxiety behavior of local administration of THC in the prefrontal cortex, basolateral amygdala and ventral hippocampus, brain regions belonging to the emotional circuit and containing high levels of CB1 receptors. THC microinjected at low doses in the prefrontal cortex (10 microg) and ventral hippocampus (5 microg) induced in rats an anxiolytic-like response tested in the elevated plus-maze, whilst higher doses lost the anxiolytic effect and even seemed to switch into an anxiogenic profile. Low THC doses (1 microg) in the basolateral amygdala produced an anxiogenic-like response whereas higher doses were ineffective. All these effects were CB1-dependent and closely linked to modulation of CREB activation. Specifically, THC anxiolytic activity in the prefrontal cortex and ventral hippocampus was paralleled by an increase in CREB activation, whilst THC anxiogenic response in the basolateral amygdala was paralleled by a decrease in CREB activation. Our results suggest that while a mild activation of CB1 receptors in the prefrontal cortex and ventral hippocampus attenuates anxiety, a slight CB1 receptor stimulation in the amygdala results in an anxiogenic-like response. The molecular underpinnings of these effects involve a direct stimulation of CB1 receptors ending in pCREB modulation and/or a possible alteration in the fine tuning of local neuromodulator release.
Comparable studies
Other preclinical and animal studies on anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Chronic, Intermittent Microdoses of the Psychedelic N , N -Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents Male rats | 2019 | Animal study | |
| 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning Mice | 2015 | Preclinical experimental study | |
| Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline Male mice exposed to chronic restraint stress | 2022 | Preclinical experimental study |
Citations in the library
Cited by 17
- Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties Journal of Translational Medicine October 2, 2020
- Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia Translational Psychiatry November 27, 2012
- Δ-9-Tetrahydrocannabinol and Cannabidiol produce dissociable effects on prefrontal cortical executive function and regulation of affective behaviors Neuropsychopharmacology November 27, 2018
- Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis Psychopharmacology October 13, 2022
- Central Executive Network drives delta-9-tetrahydrocannabinol (THC)-induced nonlinear changes in large-scale functional connectivity in adolescent nonhuman primates. Neuropsychopharmacology October 1, 2025
and 12 more in the library
Cites 2
- Cellular mechanisms underlying the anxiolytic effect of low doses of peripheral Delta9-tetrahydrocannabinol in rats. Neuropsychopharmacology September 2007
- Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. Journal of Pharmacology and Experimental Therapeutics July 2006