Effects of intracerebroventricular pirenzepine on muscarinic discriminations in rats.

In rats, mixed M1/M2 muscarinic ligands induce a discrimination which is of central origin and selectively mediated by either one or both muscarinic receptor subtypes. In the present study we examined the effects of intracerebroventricular (i.c.v.) pirenzepine, a relatively selective M1 receptor antagonist which does not cross the blood-brain barrier, on muscarinic discriminations. Groups of six rats were trained to discriminate, in a two-lever operant task, either 0.062 mg/kg subcutaneous (s.c.) scopolamine or 0.075 mg/kg s.c. oxotremorine. When the rats had been well trained in the procedure, the discriminative effects of various i.c.v. muscarinic ligands were examined. Scopolamine (1.5-12 micrograms i.c.v.), but not pirenzepine (20-40 micrograms i.c.v.), generalized to s.c. scopolamine. Oxotremorine (0.75-6 micrograms i.c.v.) generalized to s.c. oxotremorine. Scopolamine (12 micrograms i.c.v.), but not pirenzepine (20-40 micrograms i.c.v.), antagonized the oxotremorine cue. These results suggest that activation of the M1 receptor is not the prominent component of muscarinic stimulus control.