Self-injection of amphetamine directly into the brain

Abstract

Rats learned to self-administer d-amphetamine (10 micrograms/microliter) through a cannula implanted in the nucleus accumbens. They responded more frequently for 65 +/- 15 nl of amphetamine than for equal amounts of saline. When presented with two levers (one amphetamine, one blank) they responded more on the correct lever for amphetamine. They would also switch levers, when necessary, to maintain access to the drug. When half the usual drug intake was given automatically, animals reduced their response rate by half, thus self-regulating the total amount of amphetamine they received. In tests for leakage into the ventricles, eight rats that self-injected with an accumbens cannula showed response extinction when switched to a ventricular cannula. We conclude that amphetamine self-injected into the accumbens is a positive reinforcer. This localization of 'amphetamine reward' suggests that the nucleus accumbens contains a synaptic mechanism underlying amphetamine abuse and, perhaps, also natural reinforcement of behavior.

Two Brain Sites for Cannabinoid Reward

“…The present data confirm that cannabinoids have reinforcing effects in the same brain regions implicated in opiate [posterior VTA (Zangen et al, 2002)] and stimulant [NAS (Hoebel et al, 1983;Carlezon and Wise, 1996)] addiction, and that these effects are dependent on CB 1 R activation. The fact that ⌬9 THC in these brain regions can establish self-administration habits in lower animals fits well with previous observations that ⌬9 THC is selfadministered intravenously by squirrel monkeys (Tanda et al, 2000), that it potentiates the rewarding effects of direct electrical stimulation of reward pathways in rats , and that it, like other drugs of abuse (Di Chiara and Imperato, 1988), activates mesolimbic dopamine neurons (French, 1997) causing release of dopamine in nucleus accumbens (Ng Cheong Ton et al, 1988;Tanda et al, 1997).…”

“…This approach has been used to determine that amphetamine (Hoebel et al, 1983), morphine (Olds, 1982), and phencyclidine (Carlezon and Wise, 1996), have rewarding actions in nucleus accumbens (NAS; where the majority of the fibers of the mesolimbic dopamine system terminate) and that nicotine (Laviolette and van der Kooy, 2003) and -and ␦-opioids (Bozarth and Wise, 1981;Olds, 1982;Devine and Wise, 1994;Zangen et al, 2002) have rewarding actions in the ventral tegmental area (VTA; the origin of the mesolimbic dopamine system). These agents are thought to be habit-forming because they activate the mesolimbic dopamine system or because they act on GABAergic neurons that receive input from or send output to the dopamine system (Wise, 1998).…”

Subthalamic Nucleus Lesions Enhance the Psychomotor-Activating, Incentive Motivational, and Neurobiological Effects of Cocaine

“…This is not solely the result of the aversive effects of high doses. Thus, even when drug is directly self-administered into the nucleus accumbens, animals self-regulate their intake (Hoebel et al, 1983). These findings are difficult to explain purely in terms of the incentive motivational properties of drugs of abuse, leading some to speculate that drugs of abuse simultaneously activate an inhibitory process that decreases operant responding (Ettenberg and Geist, 1993;Kiyatkin and Stein, 1995;Winstanley et al, 2003).…”

Anxiogenic-Like Effects Limit Rewarding Effects of Cocaine in BALB/cByJ Mice

“…Ibotenic acid lesions of an output of the NAc shell, the sublenticular ventral pallidum, decrease responding for intravenous cocaine (Hubner and Koob 1990;Robledo and Koob 1993). Moreover, amphetamine, cocaine, and nomifensine as well as D1 and D2 dopaminergic agonists are self-injected into this subregion (Hoebel et al 1983;Carlezon et al 1995;Ikemoto et al 1997;McKinzie et al 1999). A core placement could explain the negative results reported by an early study looking at cocaine intra-NAc self-administration in rats (Goeders et al 1983).…”