Induction of self-maintained intoxication in ethanol-dependent rats

105

acid decarboxylase. The high-performance liquid chromatography method we have utilized allows simultaneous determination of DOPA, DA and DOPAC (dihydroxyphenylacetic acid) levels. Male C57B1 mice exposed for seven days to a liquid diet containing 7% ethanol and withdrawn for 24 hours had a significantly decreased rate of striatal DA synthesis, as compared to controls. The stimulation of DA synthesis by morphine sulfate was also significantly reduced in the ethanol-withdrawn mice. No differences were found between ethanol-withdrawn and control animals in the amount of morphine reaching the striatum after peripheral injection. Studies of the specific binding of [3H-] dihydromorphine to striatal tissue revealed a biphasic Scatchard plot, suggesting the presence of two opiate binding sites. The KD of the higher-affinity site was increased in the ethanol-withdrawn animals. There was no significant change in the number of binding sites, although the ethanol-withdrawn animals tended to have an increased number of sites. No significant changes were observed in the low-affinity site. Thus, in the ethanol-withdrawn animals, the decreased response of DA synthesis to a submaximal dose of morphine may well result from the decreased affinity of the opiate receptor. The time course of these changes following ethanol withdrawal is under investigation. A similar change in the K, for dihydromorphine has been observed in the mouse striatum at 24 hours after an acute (3 g/kg) dose of ethanol, suggesting that a rapid adaptive response to the perturbing effect of ethanol may occur with respect to these opiate receptors. The changes in opiate receptor function may be indicative of the adaptive changes which are related to the development of acute and/or chronic tolerance to this drug. Supported in part by grants from NIAAA (AA-2696), NIDA (DA-2024 and 1951), the Veterans Administration and by the State of Illinois DMH& DD (8083-13). S.U. is a Swiss National Science Foundation Fellow. 112 INDUCTION DEPENDENT

OF SELF-MAINTAINED RATS

P. MARFAING-JALLAT*

INTOXICATION

IN ETHANOL-

and J. LE MAGNEN

Laboratoire de Neurophysiologie Sensorielle et Comportementale, Place Marcelin Berthelot, 75231 Paris Cedex 05 (France)

Coildge de Fmnce.

1I

It is well known that naive rats refuse to drink alcohol solutions beyond their oxidative capacity which appears as a limiting factor of their oral intake of ethanol. Thus, the induction of physical dependence through spontaneous oral intake is prevented. In rats made physically dependent by forced administration of ethanol, we have previously shown that alleviation of the withdrawal syndrome by ethanol may reinforce a taste preference for ethanol. However, the induction of a true behavioral dependence in such rats is not easily obtained. A procedure has been developed which allowed the condi-

106 tioning of a consistent high voluntary oral intake of ethanol in previously intoxicated rats. Rats bearing an intragastric (i.g.) catheter received five automatically monitored daily i.g. administrations of 2 g/kg ethanol for 8 consecutive days. Eighteen hours after the cessation of treatment, the rats were offered, as the only source of fluid, either an ethyl alcohol solution (10%) or water in alternation for 30 min every 6 hours. Control rats were administered saline i.g. and submitted to the same post treatment schedule of alternate fluid presentations. After 8 days, experimental and control rats were offered a free choice between ethyl alcohol solution and water during 24 hours. The daily intake of ethanol during the alternate presentation averaged 11.06 g/kg and 72.63% of the total fluid intake, versus 2.43 g/kg and 24.88% in control rats. During the nocturnal presentation of ethanol, the oral intake reached 7.81 g/kg in intoxicated rats. During the free-choice presentation, ethanol-dependent rats, compared to naive rats, exhibited a sustained preference for ethanol versus water with a daily intake averaging 6.08 g/kg versus 2.93 g/kg. The efficacy of this procedure in inducing self-maintained intoxication is discussed. It is attributed to the periodic reinstatement of the withdrawal state which favors at each presentation of the ethanol solution the positively reinforcing effect of alcohol. 113 ACUTE AND CHRONIC PEPTIDE OPIATES KENNETH BLUM*, MADHABANANDA

INTERACTIONS

BETWEEN

ETHANOL

ARTHUR H. BRIGGS, STEVE F. A. ELSTON, SAR and PETER SHERIDAN

University of Texas Health Science Center, San Antonio, North Carolina, Chapel Hill, NC 27514 U.S.A.

TX 78284

AND

LEO DELALLO, and University

of

Previous work from our laboratory showed opiate-like activity for ethanol and the isoquinoline salsolinol on the field stimulated mouse vas deferens. We now report additive effects between normorphine (3.3 - 10 X lo-* M) and D-Ala2-methionine enkephalin (D-Al-Met-Enk) at 5.1 - 15.3 X 10pl’ M and ethanol (5 - 15 X 10e4 M) on both the mouse (ICR Swiss) vas deferens and guinea-pig ileum, typical opiate-sensitive tissue preparations. Similar additive effects were also found with salsolinol (2.6 X 10e6 M) and D-Al-Met-Enk (2.1 - 6.4 X lo-’ M) on the electrically stimulated guinea-pig ileum. Chronic studies were performed with ICR Swiss mice allowed to imbibe a Sustacal liquid diet containing 10.62% ethanol over a 5-day period. Vas deferens obtained from the ethanol-treated group had a significantly reduced baseline tension (48% reduction, p < 0.01) compared to paired controls. In this regard, it was observed that vas deferens obtained from the alcohol group showed marked supersensitivity to norepinephrine-induced contractions at the peak withdrawal time of 4 hours. However, stimulated mouse vas deferens obtained from ethanol-treated mice at either 0, 4 or 48