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Brain ethanol concentrations and ethanol discrimination in rats: effects of dose and time

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Abstract

Rationale

In drug discrimination procedures, the substitution pattern for ethanol of various receptor ligands is dependent upon ethanol training dose, presumably reflecting functionally different concentrations of ethanol in the brain. The discriminative stimulus effects of ethanol are also time-dependent, although very few studies have investigated the time course of ethanol discriminations.

Objectives

The present study investigated the relationship between brain ethanol concentrations (BrEC), as measured by intracranial microdialysis of the nucleus accumbens, and the time course of ethanol discriminative effects.

Methods

Two groups of rats were trained to discriminate either 1.0 or 2.0 g/kg ethanol from water following a 30-min post-ethanol interval. Following training, the time course of the discriminative stimulus was assessed using a series of abbreviated testing trials at 20-min intervals for 5 h after the administration of various ethanol doses (0, 0.5, 1.0 and 2.0 g/kg). The rats were then fitted with microdialysis probes and the time course of BrECs were determined under conditions similar to the behavioral assessments.

Results

BrECs were significantly above zero at 4 min post-gavage and attained peak concentrations of 16 mmol/l, 24 mmol/l and 42 mmol/l at 9 min, 16 min and 95 min after IG administration of 0.5, 1.0 and 2.0 g/kg ethanol, respectively. BrECs were similar in ethanol-naive and ethanol-trained rats, indicating a lack of pharmacokinetic tolerance under these discrimination procedures. The discriminative stimulus effects of ethanol were dose- and time-dependent, with a threshold concentration of approximately 12 mmol/l achieved at 5 min after 1.0 g/kg ethanol gavage in rats trained to discriminate 1.0 g/kg ethanol. Acute tolerance to the discriminative stimulus effects of ethanol was evident from BrECs 2–5 h post-ethanol gavage.

Conclusions

Ethanol given intragastrically results in a rapid increase in BrEC, independent of ethanol exposure history. The discriminative stimulus effects of ethanol trained at 30 min post-gavage reflect a specific range of BrEC, and depend on the training dose. These data suggest that qualitatively different stimulus effects of ethanol reflect both different ranges of BrEC, as well as within dose acute tolerance to the discriminative stimulus effects.

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References

  • Ferraro TN, Weyers P, Carrozza DP, Vogel WH (1990) Continuous monitoring of brain ethanol levels by intracerebral microdialysis. Alcohol 7:129–132

    CAS  PubMed  Google Scholar 

  • Gill K, Deitrich RA (1998) Acute tolerance to the ataxic effects of ethanol in short-sleep (SS) and long-sleep (LS) mice. Psychopharmacology 136:91–98

    Article  CAS  PubMed  Google Scholar 

  • Grant KA (1999) Strategies for understanding the pharmacological effects of ethanol with dug discrimination procedures. Pharmacol Biochem Behav 64:261–267

    PubMed  Google Scholar 

  • Grant KA, Colombo G (1992) Discriminative stimulus effects of ethanol: effects of training dose on the substitution of N-methyl-d-aspartate antagonists. J Pharmacol Exp Ther 264:1241–1247

    Google Scholar 

  • Grant KA, Colombo G (1993a) Pharmacological analysis of the mixed discriminative stimulus effects of ethanol. Alcohol Alcohol Suppl 2:445–449

    CAS  PubMed  Google Scholar 

  • Grant KA, Colombo G (1993b) Substitution of the 5-HT1 agonist trifluoromethylphenylpiperazine (TFMPP) for the discriminative stimulus effects of ethanol: effects of training dose. Psychopharmacology 113:26–30

    Google Scholar 

  • Grant KA, Colombo G, Gatto GJ (1997) Characterization of the ethanol-like discriminative stimulus effects of 5-HT receptor agonists as a function of ethanol training dose. Psychopharmacology 133:133–141

    Google Scholar 

  • Green KL, Grant KA (1998) Evidence for overshadowing by components of the heterogeneous discriminative stimulus effects of ethanol. Drug Alcohol Depend 52:149–159

    PubMed  Google Scholar 

  • Hiltunen AJ, Jarbe TU (1992) Acute and chronic ethanol tolerance: operant behaviour in naive and ethanol tolerant rats. Psychopharmacology 107:511–516

    CAS  PubMed  Google Scholar 

  • Kalant H (1988) Research on tolerance: what can we learn from history? Alcohol Clin Exp Res 22:67–76

    Google Scholar 

  • Le AD, Mana M, Quan B, Kalant H (1992) Differential development of acute tolerance to the motor impairment and anticonvulsant effects of ethanol. Psychopharmacology 109:107–111

    CAS  PubMed  Google Scholar 

  • Levitt MD, Furne J, DeMaster EG (1994) Magnitude, origin, and implications of the discrepancy between blood ethanol concentrations of tail vein and arterial blood of the rat. Alcohol Clin Exp Res 18:1237–1241

    CAS  PubMed  Google Scholar 

  • Lumeng L, Li TK (1986) The development of metabolic tolerance in the alcohol-preferring P rats: comparison of forced and free-choice drinking of ethanol. Pharmacol Biochem Behav 25:1013–1020

    Article  CAS  PubMed  Google Scholar 

  • Lyons D, Miller MD, Hedgecock-Rowe AA, Crane AM, Porrino LJ (1998) Time-dependent effects of acute ethanol administration on regional cerebral blood flow in the rat. Alcohol 16:213–219

    Google Scholar 

  • Nurmi M, Kiianmaa K, Sinclair JD (1994) Brain ethanol in AA, ANA, and Wistar rats monitored with one-minute microdialysis. Alcohol 11:315–321

    CAS  Google Scholar 

  • Quertemont E, de Neuville J, De Witte P (1998) Changes in the amygdala amino acid microdialysate after conditioning with a cue associated with ethanol. Psychopharmacology 139:71–78

    CAS  PubMed  Google Scholar 

  • Robinson TE, Whishaw IQ (1988) Normalization of extracellular dopamine in striatum following recovery from a partial unilateral 6-OHDA lesion of the substantia nigra: a microdialysis study in freely moving rats. Brain Res 450:209–224

    CAS  PubMed  Google Scholar 

  • Sancho-Tello M, Sanchis R, Guerri C (1988) Effect of short and long-term ethanol feeding on the extent of metabolic tolerance in female rats. Alcohol Alcohol 23:483–490

    CAS  PubMed  Google Scholar 

  • Schechter MD (1989) Time-dependent effect of ethanol upon discrimination behavior. Alcohol 6:445–449

    CAS  PubMed  Google Scholar 

  • Shippenberg TS, Altshuler HL (1985) A drug discrimination analysis of ethanol-induced behavioral excitation and sedation: the role of endogenous opiate pathways. Alcohol 2:197–201

    CAS  PubMed  Google Scholar 

  • Sunahara GI, Kalant H, Schofield M, Grupp L (1978) Regional distribution of ethanol in the rat brain. Can J Physiol Pharmacol 56:988–992

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Belgian National Funds for Scientific Research (to E. Quertemont) and the National Institute of Alcohol Abuse and Alcoholism AA11997 and AA09246.

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Correspondence to Kathleen A. Grant.

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Quertemont, E., Green, H.L. & Grant, K.A. Brain ethanol concentrations and ethanol discrimination in rats: effects of dose and time. Psychopharmacology 168, 262–270 (2003). https://doi.org/10.1007/s00213-003-1437-7

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  • DOI: https://doi.org/10.1007/s00213-003-1437-7

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