Presynaptic alpha-adrenergic mediation of self-stimulation in locus coeruleus in rats treated neonatally with 6-hydroxydopamine.

Rats self-stimulating in the region of the locus coeruleus and treated neonatally with 6-hydroxydopamine (6-OHDA) injected bilaterally in the same region were tested for effects of adrenergic receptor blockers on a lever-pressing behavior to obtain the brain reward. The neonatally treated animals (16 microgram total dose, 8 microgram X 2) self-stimulated at abnormally high rates compared with controls. Yohimbine (5 mg/kg i.p.) and phentolamine (5 mg/kg) suppressed self-stimulation in controls and treated subjects. Phenoxybenzamine (10 mg/kg) reduced the response rate for the brain reward but did not abolish the behavior in the 6-OHDA-treated animals and had minor effects in controls. Propranolol (10 mg/kg) had no effects. The 6-OHDA subjects tested for the effects of D-amphetamine and L-amphetamine (0.5 mg/kg) showed facilitation of responding after the former but not after the latter. Self-stimulation in the 6-OHDA subjects was suppressed by treatment with alpha-methyl-p-tyrosine and pimozide. The significance of these findings is discussed in terms of the use of alpha-adrenoreceptor antagonists to separate the pre- from the post-synaptic action of released norepinephrine and in terms of the norepinephrine hypothesis of rewarding effects of brain stimulation in the dorsal pons.