The influence of cocaine on rat brain monoaminergic neurotransmitters (dopamine, serotonin, noradrenaline) and their metabolites, and on binding of [3H]WIN 35,428 and [3H]GBR 12,935 to the dopamine transporter was measured after 4 weeks of cocaine exposure. Cocaine (mean daily dose 9.25 +/- 0.48 mg/kg) was self-administered (responders) or passively received (yoked) during sessions which lasted for 1 h per day. As compared with the controls, mean dopamine and serotonin levels were significantly elevated (+ 107% and + 47%, respectively) in amygdala of responders, but not of yoked rats, sacrificed 1 h after the last cocaine session. Dopamine and metabolite levels were normal in all other brain areas examined, including striatum, nucleus accumbens and medial prefrontal cortex, at both 1 h and 4 weeks withdrawal from cocaine. [3H]WIN 35,428 and [3H]GBR 12,935 binding were unaltered after cocaine exposure. These data provide additional support for the involvement of the amygdala in the acquisition of drug seeking behavior associated with cocaine self-administration.