Drug Effects and Biological Responses

Although many indirect factors lead to an individual abusing drugs, a person's response to the effects of the drugs themselves contribute both to their use and abuse. These drug effects should be considered in relation to four phases of drug use: (1) initiation-consolidation, (2) maintenance, (3) repeated withdrawal and relapse, and (4) postwithdrawal. Dur ing the initiation-consolidation phase, behaviors that lead to the taking of a drug are gradually strengthened through operant and classical conditioning processes and by biochemical changes in the brain. The drug effects include a cascade of discriminative or internally appreciated drug cues (i.e., subjective effects). The presence of these cues often leads to associated autonomic responses and reports of urges in humans. These responses and urges may result in an unfolding of a sequence of behavioral and physiological events leading to continued drug consumption.

After a pattern of chronic drug use is established, individuals may become tolerant to certain effects of a drug. In addition, they may experience withdrawal effects when they stop taking a drug. Withdrawal effects are often opposite to the drug-induced state and usually involve some form of dysphoria—a state of illness and distress. Over time, withdrawal effects become associated with stimuli in the environment, as was the case for the euphoric and other direct effects of the drug. Because of operant and classical conditioning processes, these associated stimuli can then produce conditioned effects that are often characterized as urges or cravings, and that may trigger relapse.

The underlying NEUROTRANSMITTER systems within the brain, subserving these behavioral features of drug effects, are just beginning to be understood. Early RESEARCH on the neural substrates of reward in general used electrical brain stimulation as the reward. For example, Olds (1977) found that rats would press a lever to receive a brief electrical pulse to the hypothalamus; rats would press this lever to such an extent that they did not engage in consummatory reward activities such as eating and drinking. Subsequent research indicated that activation of certain systems in the brain, namely the mesolimbic and nigrostriatal dopaminergic systems, were most sensitive to brain stimulation reinforcement. Several theories have been suggested to explain the importance of the brain reward system for the survival of species (Conrad, 1950; Glick-man & Schiff, 1967; O'Donahue & Hagmen, 1967; Roberts & Carey, 1965).

Further research demonstrated that most drugs of abuse lower the threshold for this brain stimulation reward, thus suggesting that such drugs may activate the same, or similar, reward pathways (see Koob & Bloom, 1988). As will be seen, furthermore, the reinforcing effects of the drugs them selves—that is, effects that lead individuals to take the drugs—are directly mediated by these REWARD systems. The fact that many drugs induce activation of these systems may indicate a mechanism underlying the addiction-related effects of drugs of abuse.

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