# Individual differences in GHB consumption in a new voluntary GHB self-administration model in outbred rats

## TL;DR

This study introduces a new rat model for voluntary GHB consumption and finds individual differences in addiction-like behavior and memory effects.

## Contribution

A new voluntary GHB self-administration model in outbred rats that captures individual differences in addiction-like behavior.

## Key findings

- Rats consumed stable, pharmacologically relevant levels of GHB over 3 months with no clear withdrawal symptoms.
- Only a subset of rats showed high motivation and habitual GHB-seeking behavior.
- Male rats exhibited reduced long-term memory after chronic GHB use, but anxiety-like behavior was unaffected.

## Abstract

The use of the recreational drug gamma-hydroxybutyric acid (GHB) has increased over the past decade, concomitantly leading to a higher incidence of GHB use disorder. Evidence-based treatment interventions are hardly available and cognitive effects of long-term GHB use remain elusive. In order to study the development of GUD and the causal effects of chronic GHB consumption, a GHB self-administration model is required.

Long Evans rats had access to GHB in their home cage according to a two-bottle choice procedure for 3 months. Intoxication and withdrawal symptoms were assessed using an automated sensor-based setup for longitudinal behavioral monitoring. Rats were trained in an operant environment according to a fixed ratio (FR) 1, 2, and 4 schedule of reinforcement. Addiction-like behaviors were assessed through progressive ratio-, non-reinforced-, and quinine-adulterated operant tests. In addition, the novel object recognition test and elevated plus maze test were performed before and after GHB self-administration to assess memory performance and anxiety-like behavior, respectively.

All rats consumed pharmacologically relevant levels of GHB in their home cage, and their intake remained stable over a period of 3 months. No clear withdrawal symptoms were observed following abstinence. Responding under operant conditions was characterized by strong inter-individual differences, where only a subset of rats showed high motivation for GHB, habitual GHB-seeking, and/or continued responding for GHB despite an aversive taste. Male rats showed a reduction in long-term memory performance 3 months after home-cage GHB self-administration. Anxiety-like behavior was not affected by GHB self-administration.

The GHB self-administration model was able to reflect individual susceptibility for addiction-like behavior. The reduction in long-term memory performance upon GHB self-administration calls for further research into the cognitive effects of chronic GHB use in humans.

The online version contains supplementary material available at 10.1007/s00213-024-06537-5.