, Volume 64, Issue 3, pp 277–283 | Cite as

Comparison of opiate agonists and their N-allyl derivatives in the production of physical dependence in the rat

  • Max R. Fennessy
  • Frank J. Laska
Original Investigations


The development of physical dependence to slow-release (SR) emulsions of various opiate agonists and their N-allyl derivatives was examined. Rats were injected SC with SR preparations of morphine (75 mg/kg), nalorphine (75 mg/kg), oxymorphone (75 mg/kg), naloxone (75 mg/kg), levorphanol (30 mg/kg), levallorphan (75 mg/kg) or dextrorphan (75 mg/kg), and behaviour was assessed for 24 h. Only morphone, oxymorphone and levorphanol induced signs typical of opiate intoxication lasting 12 h or more. After 24 h the rats were challenged with injections of naloxone (5 mg/kg IP) and withdrawal behaviour and changes in body temperature and body weight were estimated. Withdrawal symptoms were exhibited to varying degrees by all rats except those which had received naloxone SR. Only rats which were injected with the agonists exhibited both jumping and wetshake responses. Falls in body temperature and body weight appeared to be associated with withdrawal, but it was difficult to differentiate between the opiate agonists and their N-allyl derivatives. In other groups of rats, the brain levels of noradrenaline (NA), dopamine (DA), homovanillic acid (HVA), 5-hydroxytrypamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured spectrofluorimetrically 24 h after administration of the SR preparations. Apart from levorphanol SR, which increased brain DA and HVA, none of the drugs affected the levels of NA, DA, HVA and 5-HT. However, all drugs significantly increased the brain levels of 5-HIAA. The opiate agonists increased the level of this metabolite to a significantly greater extent than their corresponding N-allyl derivative. It is concluded that opiate agonists induce a greater degree of physical dependence than their N-allyl derivatives. In addition, since dextrorphan is as effective as the agonists in producing several of these effects, it appears that changes in body temperature and body weight and alteration of the metabolism of brain 5-HT may not be causally related to the dependence process induced by opiates. Such modifications may be associated with the structure of the opiate molecule.

Key words

Opiate agonists N-allyl derivatives Physical dependence Hypothermia Body weight Brain amines 


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Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Max R. Fennessy
    • 1
  • Frank J. Laska
    • 1
  1. 1.Department of PharmacologyUniversity of MelbourneParkvilleAustralia

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