In order to further characterize the pharmacologic mechanisms that mediate the antipsychotic drug-induced increase in neurotensin (NT) in nucleus accumbens and striatum, the effects of three weeks treatment with psychotherapeutic levels of lithium alone or in conjunction with haloperidol were compared to the ability of haloperidol alone to alter NT and neuromedin N (NMN) regional brain concentrations in rats. A separate experiment examined the ability of a selective dopamine D2 receptor agonist, quinelorane, to alter NT/NMN regional concentrations after three weeks of treatment as compared to haloperidol, a D2 receptor antagonist. Haloperidol (1 mg/kg) increased both NT and NMN concentrations in several brain regions and these parallel peptide increases were highly correlated. Lithium chloride (0.4 mM) had no effect, either alone or with haloperidol, on NT/NMN concentrations. Quinelorane (1 mg/kg), however, effectively increased both NT and NMN concentrations in the caudate nucleus and nucleus accumbens, as did haloperidol (2 mg/kg). These data indicate that the induction of NT and NMN, whose adjacent sequences are contained in a pro-hormone product of a single gene, occurs in tandem and remains proportional, as well as demonstrating that putative D2 receptor agonists can produce effects on NT/NMN systems that are similar to D2 receptor antagonists.