The effects of apomorphine and d-amphetamine on striatal c-Fos expression in Sprague–Dawley and Long Evans rats and their F1 progeny

We previously reported that Sprague–Dawley (SD) rats are significantly more sensitive than Long Evans (LE) rats to disruption of prepulse inhibition (PPI) of the startle reflex by the dopamine agonists, apomorphine (APO) and d-amphetamine (AMPH). This susceptibility is inherited through F1 (SD × LE) and N2 backcross (F1 × SD) generations via an orderly pattern (SD > N2 > F1 > LE). Here we examined systemic APO (0.5 mg/kg) and AMPH (4.5 mg/kg) modulation of neural activity in four regions of the striatum suspected to be involved in the dopaminergic regulation of PPI – dorsolateral (dlCPu) and medial (mCPu) caudate/putamen and core (NACc) and medial shell (NACms) regions of nucleus accumbens – under conditions that mimicked those used to assess PPI. Immunohistochemical quantification of c-Fos protein expression was used as the surrogate measure of neural activity in SD and LE rats and their F1 crosses. Vehicle-treatment showed significant regional differences in Fos expression, particularly between the dlCPu and the other three areas, but no strain-related differences were observed. Three of four brain areas examined (dlCPu, mCPu and NACc) exhibited drug-induced changes in Fos expression—APO decreased and AMPH increased Fos expression in each region. The aggregate effect across these three regions revealed Fos expression to be significantly greater in LE compared to SD rats for both drugs, with F1 rats intermediate. This pattern of inheritance (LE > F1 > SD) reveals an inverse relationship between striatal Fos expression and PPI sensitivity for these drugs; and a positive relationship with reported heritable differences in D2-linked G-protein binding in the CPu and NACc, and with locomotor activation/suppression by AMPH and APO.