Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Δ9-tetrahydrocannabinol

Daina Economidou, Laura Mattioli, Massimo Ubaldi, Anbarasu Lourdusamy, Laura Soverchia, Gary Hardiman, Patrizia Campolongo, Vincenzo Cuomo, Roberto Ciccocioppo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

The present study evaluated the consequences of perinatal Δ9-tetrahydrocannabinol (Δ9-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB1 receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with Δ9-tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, Δ9-THC, or EtOH + Δ9-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to Δ9-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB1 receptor antagonists may represent interesting agents for the pharmacotherapy of alcoholism.

Original languageEnglish
Pages (from-to)73-85
Number of pages13
JournalToxicology and Applied Pharmacology
Volume223
Issue number1
DOIs
Publication statusPublished - 15 Aug 2007
Externally publishedYes

Keywords

  • Δ-Tetrahydrocannabinol
  • Ethanol reinstatement
  • Gene expression
  • Microarray
  • Perinatal treatment
  • SR-141716A

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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