Methamphetamine-induced expression of zif268 mRNA is prevented by haloperidol in mice lacking mu-opioid receptor

Abstract

We investigated the role of mu-opioid receptor (mu-OR) and dopamine receptor in the modulation of methamphetamine (METH)-induced expression of zif268 mRNA in the striatum of mice. Four groups of wild-type and mu-OR knockout mice were given a single daily intraperitoneal injection of saline (control; group 1) or METH (10mg/kg; groups 2-4) for 7 consecutive days. On day 11 (after 4 abstinent days), groups 1 and 2 were challenged with saline, group 3 was challenged with METH (10mg/kg), and group 4 was challenged with dopamine receptor antagonist haloperidol (0.06 mg/kg, subcutaneous injection) plus METH (10mg/kg). Two hours after the last saline or METH injection, mouse brain tissues were taken for zif268 mRNA analysis using in situ hybridization histochemistry. In comparison to corresponding saline control group (group 1), striatal zif268 mRNA levels were unchanged in group 2 and increased in group 3 in both wild-type and mu-OR knockout mice and without genotype difference. METH challenge-enhanced expression of zif268 mRNA was completely abolished by pre-administration of haloperidol (group 4) in mu-OR knockout mice but not in wild-type mice. The results suggest a crosstalk of the two neurotransmitter systems in modulation of METH-induced IEG expression, because only in mu-OR knockout mice in which dopamine receptors were blocked were METH-induced zif268 expression abolished. METH-induced zif268 expression was not altered in mu-OR knockout mice without blockade of dopamine receptors or wild-type mice with blockade of dopamine receptors.

Figure 1

In situ film autoradiograms showing the expression of zif268 mRNA in the brain slides from the wild type and μ-OR knockout mice. Mice were daily intraperitoneally (i.p.) injected with saline (control; group 1) or METH (10 mg/kg; group 2–4) for 7 consecutive days. On day 11, each group of mice was subcutaneously (s.c.) injected with saline (groups 1–3) or haloperidol (0.06 mg/kg; group 4) and then, 30 min later, injected with saline (groups 1 and 2) or METH (10 mg/kg, i.p.; groups 3 and 4). Two hours following the last injection, mice were sacrificed by decapitation. The brain tissues were reserved for preparation of brain sections and in situ hybridization analysis.