Amphetamine and morphine may produce acute-withdrawal related hypoactivity by initially activating a common dopamine pathway

- Longer-term hypoactivity (LH) is a reduction in activity 12-24 h following drug.
- LH is a sign of acute withdrawal.
- Amphetamine (Amph) and morphine (Morph) given every 5 days elicit similar LH.
- The LH elicited by both drugs was blocked by co-administration of a D1 antagonist.
- Amph and Morph elicit some signs of withdrawal via a common dopamine pathway.

Rats given drugs of abuse such as amphetamine or morphine show longer-term effects, that is, signs of acute withdrawal, including hypoactivity, hypophagia, and blunted affect, sometime between 12 and 24 h after treatment. This research explores the possibility that signs of acute withdrawal produced by different drugs of abuse are instigated by overlapping mechanisms. The specific objectives of the research were to see if amphetamine and morphine produced longer-term hypoactivity, and to see if any longer-term hypoactivity elicited by the drugs could be blocked by SCH23390, a dopamine D1 antagonist. Six groups of rats, with eight rats in each group, were exposed to a series of five-day tests. Near light onset of Test Day 1, each animal was given control administrations, consisting of a saline treatment (1.0 ml/kg) followed 30 m later by a saline posttreatment, and locomotor activity was monitored for the next 24 h. On Test Day 3, each animal was given experimental administrations, and locomotor activity was again monitored for 24 h. Each group received only one combination of experimental administrations across tests. Experimental administrations consisted of saline, amphetamine (2.0 mg/kg), or morphine (5.0 mg/kg), followed by saline or SCH23390 (0.05 mg/kg). All administrations were subcutaneous. Amphetamine and morphine produced longer-term hypoactivity, having similar time courses and magnitudes. SCH23390 blocked the longer-term hypoactivity produced by both drugs. Saline and SCH23390 produced no changes in longer-term activity in their own right. The time course of amphetamine-elicited longer-term hypoactivity resembled that of amphetamine-elicited longer-term hypophagia observed in a prior study. Approximately 1/4 of the animals given amphetamine or morphine did not show longer-term hypoactivity (“low withdrawal” rats). Amphetamine and morphine may initiate the cascade of events resulting in signs of acute withdrawal by producing activation in a common pathway that uses dopamine as a neurotransmitter. Different signs of acute withdrawal (hypoactivity and hypophagia) may involve the short-term activation of the same common pathway. Low withdrawal rats may have a different vulnerability to amphetamine and may show differences in drug assessment outcomes relative to animals that manifest distinct signs of acute withdrawal.