Pharmacological Modulation of Noradrenergic Signaling

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) was prepared in saline solution and injected IP in a single dose of 50 mg/kg (2958; Tocris). This dose was selected based on previous studies showing tissue NE depletion in the brain [19 (link)]. Three days after DSP-4 treatment, stereotaxic injection of 6OHDA or rAAV2–hα-SYN injection was performed as described above. To block the norepinephrine transporter (NET), we use Desipramine (D3900; Sigma). A single dose of Desipramine (25 mg/kg in saline solution) was delivered IP 45 min prior to DSP-4 treatment. Propranolol was delivered IP daily at 10 mg/kg in saline solution (0624; Tocris). Propranolol treatment started 45 min after stereotaxic injection of rAAV2–hα-SYN injection and was given once a day until the end of the experiment. Xamoterol (3 mg/kg; IP) (24,267; Cayman) and Clenbuterol (10 mg/kg; IP) (C5423, Sigma) daily treatment was performed beginning 45 min after stereotaxic injection of rAAV2–hα-SYN injection for 4 weeks until the end of the experiment. All drugs used here were dissolved fresh using saline solution the day of treatment and saline solution was used as vehicle control in all experimental conditions. Clenbuterol and xamoterol doses were selected based on previous studies related to CNS pathologies [16 (link), 20 (link)].