Time course of tyrosine hydroxylase expression after behavioral sensitization to cocaine

Levels of tyrosine hydroxylase (TH) immunoreactivity and mRNA in the ventral tegmental area (VTA) and TH immunoreactivity in the nucleus accumbens were measured after early (24 hr) and late (3 weeks) withdrawal times from acute and repeated cocaine treatment. Two doses of cocaine (15 mg/kg i.p. or 30 mg/kg i.p.) were administered for 6 days to produce behavioral sensitization to a cocaine challenge either 24 hr later or three weeks later. At the early withdrawal time, TH immunoreactivity and TH mRNA levels were measured 2 or 24 hr after the cocaine or saline challenge, and at the late withdrawal, measurements were made 24 hr after the challenge. At early withdrawal, after both doses of repeated cocaine treatment, TH immunoreactivity in the VTA increased to 125% of saline controls by 24 hr after the cocaine challenge, with no significant changes in TH mRNA levels at either 2 or 24 hr after the cocaine challenge. Measures of basal tyrosine hydroxylation levels in the VTA 24 hr after cocaine challenge revealed no significant changes after daily cocaine pretreatment. At the late withdrawal time, levels of TH immunoreactivity or mRNA in the VTA were not statistically altered 24 hr after a saline or cocaine challenge. In the nucleus accumbens, TH immunoreactivity was not altered at any of the times measured. The data do not indicate a clear association between the regulation of TH expression and enduring behavioral sensitization to daily cocaine pretreatments. However, the time course of TH expression in the VTA parallels previously reported changes in somatodendritic dopamine release and autoreceptor desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)