Decreasing brain activity caused by acute administration of ketamine and alcohol - A randomized, controlled, observer-blinded experimental study.
Luan Oliveira Ferreira, Esther Padilha da Silveira, Clarissa A Paz, Maria K Otake Hamoy, Gabriela B Barbosa, Murilo F Santos, Raína M Conceição, Anthony Lucas G Amaral, Karina Dias Resende, Dielly Catrina Favacho Lopes, Moisés Hamoy
Frontiers in Pharmacology 2024 DOI: 10.3389/fphar.2024.1456009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Randomized Peer reviewed |
|---|---|
| Sample size | 72 |
| Population | Late-adolescent (8-10-week-old) male Wistar rats |
| Interventions | Ketamine Alcohol |
| Dose | low (10 mg/kg), intermediate (20 mg/kg) or high (30 mg/kg) ketamine via intraperitoneal injection; alcohol (2 mL/100 g) via oral gavage |
| Topics | Addiction Ketamine Esketamine |
| Keywords | Alcohol-related disorders Brain waves Electroencephalography Substance-related disorders Drug abuse Substance dependence Neuroscience brain science Neural activity Brain research Pharmacological interactions Substance mixing |
| Key findings | Ketamine enhances alcohol's depressant effect on alpha brainwaves at all doses, but a low dose intensifies suppression of theta and beta waves while a high dose produces neuronal hyperexcitability in theta and gamma bandpower. |
Abstract
Substance abuse is a major public health problem. In recent years, ketamine, which is a parenteral anesthetic, has been consumed increasingly as an illicit drug together with alcohol, although little is known of how this association alters brain activity. The present study investigated the influence of progressive doses of ketamine, associated with alcohol, on electrophysiological activity. For this, 72 late-adolescent (8-10-week-old) male Wistar rats received either ketamine only, at low (10 mg/kg), intermediate (20 mg/kg) or high (30 mg/kg) doses via intraperitoneal injection, or alcohol (2 mL/100 g) via oral gavage followed by ketamine (at low, intermediate, and high doses). Electroencephalograms (EEG) and electromyographic recordings were obtained 5 min after the final application of the drug. When administered alone, ketamine resulted in an increase in delta, theta, beta, and gamma brainwaves, with a more pronounced effect being detected at the highest dose (30 mg/kg) in the case of the delta, beta, and gamma waves. The amplitude of the alpha brainwaves was reduced at all doses of ketamine, but less intensively at the highest dose. When administered alone, alcohol reduced all the brainwaves, with the reduction in the alpha waves being exacerbated by ketamine at all doses, and that of the theta and beta waves being boosted at the lowest dose. The intermediate dose of ketamine (20 mg/kg) reverted the alcohol-induced reduction in the theta and gamma waves, whereas the high dose increased delta, theta, beta, and gamma bandpower. Overall, then, while ketamine enhances the depressant effects of alcohol on the alpha brainwave at all doses, a low dose intensified this effect on the theta and beta 175 waves, whereas a high dose produces neuronal hyperexcitability in the theta and 176 gamma bandpower.
Comparable studies
Other preclinical and animal studies on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| R-(-)-ketamine modifies behavioral effects of morphine predicting efficacy as a novel therapy for opioid use disorder. Morphine-dependent rats and mice | 2020 | Preclinical study | |
| The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement. Male and female oxycodone-dependent mice | 2023 | Preclinical study | |
| Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile. Adolescent rats of both sexes, including naïve and early-life stressed (maternal... | 2025 | Preclinical study | |
| Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats. Long Evans rats | 2024 | Preclinical experimental study | |
| Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way. Male and female mice with forebrain ASM overexpression | 2025 | Experimental study |