Abstract: Preclinical studies in mice and rats based on three microinfusions (12 hours apart) of specifically designed and synthesized adenosine A.sub.1 receptor antisense oligonucleotide with the sequence: (A.sub.1 Antisense: 5'-GGCCGAGATGGAGGGCGGCAT-3' (SEQ ID NO: 1)) and as a control, a mismatched antisense nucleotide with a sequence: (A.sub.1 Sense: 5'-ATGCCGCCCTCCATCTCGGCC-3' (SEQ ID NO: 1)) established that the "functional knock out" of A.sub.1 receptors protected the animals from the well known motor incoordination due to alcohol or .DELTA..sup.9 -tetrahydrocarnabinol(THC: the major psychoactive component of marijuana intake). The motor coordination in animals was evaluated by the mouse/rat rotorod treadmill. The antisense was microinfused in mouse cerebellum and in the rat motor cortex whereas ethanol was always administered systemically. However, unlike ethanol, the .DELTA..sup.9 -THC was microinfused into the mouse cerebellum following the cerebellar pretreatment with the antisense.