Changes in fixed-interval behavior during chronic morphine treatment and morphine abstinence in rats.

Rats previously trained to a fixed-interval schedule (FI 2 min) were treated twice daily with saline or morphine hydrochloride (final dose 40 mg/kg i.p.) for 44 days. On day 45 an abstinence state was induced by withdrawing morphine or by giving nalorphine (1 mg/kg i.p.). Operant behavior was recorded on alternate days during the period of chronic treatment and during the withdrawal phase (21 days). It was found that the number of lever presses decreased significantly during the first days of morphine administration but increased later over the control values. The quarter-life was not changed during this period. Morphine withdrawal and nalorphine treatment both caused a further increase in lever presses that lasted about 11 days. Again quarter-life was not changed. These results indicate that the effects of morphine on FI behavior in rats not only undergo tolerance but are actually reversed during the chronic treatment. The data obtained during the withdrawal phase are discussed in relation to the secondary abstinence syndrome described by Martin et al. (1963).