The influence of acetylcholine, a major neurotransmitter in the central nervous system (CNS), on neuropeptidergic systems is largely unexplored. Furthermore, the functional role played by the tachykinins, a family of neuroactive peptides with the consensus sequence -Phe-X-Gly-Leu-Met-NH$\sb2$ and closely associated with cholinergic neurons, is not well understood. Thus, the major goal of this dissertation research is to determine whether and how cholinergic systems regulate expression of tachykinin genes in the CNS In situ hybridization and immunocytochemical techniques were used to map the location of the tachykinin, neurokinin B-(NKB) mRNA and NKB-like immunoreactivity (-ir) in the rat CNS. The distribution of NKB resembles the distribution of another tachykinin, substance P(SP), but is most different in several locations (cerebral cortex, basal forebrain, basal ganglia, diencephalon and hindbrain). The interaction between the cholinergic- and neuropeptidergic-systems was examined by administrating systemically (s.c.) physostigmine (an indirect cholinergic agonist) at a dosage regimen of 0.4 mg/kg, 3x day, 6 d and scopolamine (a muscarinic antagonist: 0.5 mg/kg, 3x day, 6 d). SP-mRNA and (PPE) preproenkephalin-mRNA levels increased by at least 24% (p $<$ 0.01) in the dorsal striatum (CPu) after scopolamine administration. Physostigmine treatment also resulted in a 29% increase (p $<$ 0.01) in PPE-mRNA levels in the CPu. SP-mRNA levels displayed a mediolateral increase in the CPu of 42% (p $<$ 0.001) after scopolamine and a decrease of 12% (p $<$ 0.05) after physostigmine treatment as compared to control values. PPE-mRNA subregional levels did not show as large a difference between medial and lateral aspects of the CPu. In addition, an intracerebral injection of AF64A (a selective cholinotoxin) into the CPu (1 nmol/$\mu$l, 1.5 $\mu$l total volume) resulted in a decrease in the number of choline acetyltransferase-ir neurons on the side of the lesion while SP- and PPE-mRNA levels increased (by 60% and 25%, p $<$ 0.01, respectively). These data suggest that cholinergic interneurons have an inhibitory influence on striatal SP- and PPE-ergic projection neurons. Moreover, these data provide further support to the notion that the striatum is a highly compartmentalized structure that defies its morphologically homogeneous appearance
