Ritanserin overcomes exploratory inhibition induced by cocaine withdrawal

Psychostimulant withdrawal as an inducing condition in animal models of depression

“…With the use of laboratory rodents, the opportunity is provided to determine the effects of psychostimulant withdrawal in a far more controlled and intrusive manner than is possible with human studies. Hence, a large number of studies, using a wide variety of techniques, have shown convincingly that behavioral alterations, which may be linked to particular motivational states, are consistently Giorgetti et al (2000) v Touret et al (1995) w Dugovic et al (1992) x Lynch and Leonard (1978a) y Pulvirenti et al (1993) z Seltzer et al (1975) aa Paulson et al (1996) ab ac Tran-Nguyen et al (1998) ad Malin et al (2000) ae Fontana et al (1989) af Fung et al (1994) ag Sarnyai et al (1995) ah Meert TF (1992) ai Murphy et al (2001) aj Basso et al (1999) ak Harris et al (1993) al Mutschler et al (1998) am Wood et al (1987) generated during psychostimulant withdrawal in rodents. For these withdrawal-induced behavioral changes to be of relevance to human depression, they must exhibit 'construct validity', in which the behavioral changes in the animal model must be homologous, or at least analogous, to the symptoms of the disorder (Geyer and Markou, 1995).…”

“…The presence of elevated levels of anxiety during psychostimulant abstinence represents an important potential confound when utilizing the behavioral sequelae of psychostimulant withdrawal as markers of depressive symptomatology. For instance, decreases in locomotor activity that occur during psychostimulant withdrawal when a rat is exposed to a novel open field environment (Lynch and Leonard, 1978a) may reflect psychomotor retardation (a defining symptom of MDD), but could equally as well indicate increased levels of anxiety (Meert, 1992). The roles of these two factors in determining the final behavioral output may be differentially affected by a specific class of drugs, such as antidepressants, although as many compounds in this class have both antidepressant and anxiolytic properties , firm conclusions cannot always be drawn.…”

“…However, as has been discussed previously, elevated levels of anxiety appear to occur in a comorbid manner with the depressive symptomatology during psychostimulant withdrawal. Thus, drugs which exhibit anxiolytic properties, such as propanolol (Harris and Aston-Jones, 1993), ritanserin (Meert, 1992), diazepam (Paine et al, 2002) and CRF antagonists (Basso et al, 1999) all mitigate the effects of cocaine withdrawal, but only in tasks which measure anxiety, which include the conditioned defensive burying paradigm, novel field exploration and the elevated plus maze. It is unlikely that these drugs would alleviate the anhedonic deficits measured in paradigms such as ICSS responding, although this remains to be determined empirically.…”

REVIEW: Behavioral evidence for the significance of serotoninergic (5‐HT) receptors in cocaine addiction

“…In rats, amperozide restored disturbed social interactions because of withdrawal from acute cocaine exposure (Rademacher et al . 1999) while ritanserin overcame the inhibition in exploratory behavior (measured in terms of a longer latency to enter the open area, a reduction in the time spent in the open field and a decrease in the number of transits from the small dark compartment into the open area) induced by subchronic cocaine treatment for 10 days and a subsequent 24‐hour withdrawal (Meert 1992). Ritanserin also prevented the alteration in the distribution of wakefulness and deep slow wave sleep throughout the light–dark cycle, but not paradoxical sleep alterations, in rats withdrawn from daily repeated (10 days) cocaine administration (Dugovic et al .…”

Lack of depression-like effects of saccharin deprivation in rats: Forced swim test, differential reinforcement of low rates and intracranial self-stimulation procedures.

“…In laboratory animals, the decreased hedonic capacity is reflected in elevations of brain reward thresholds (i.e., decreased reward), as shown by means of the electrical brain stimulation reward procedure (Kokkinidis, Zacharko, & Anisman, 1986; Markou & Koob, 1991; Wise & Munn, 1995). Evidence also has indicated reduced motivation to obtain natural reinforcers (e.g., sucrose solution or access to a sexually receptive conspecific; Barr, Fiorino, & Phillips, 1999; Barr & Phillips, 1999), as well as reduced spontaneous and exploratory motor activity during drug withdrawal (Barr et al, 1999; Meert, 1992). Furthermore, in both human and nonhuman experimental subjects, there appears to be substantial overlap between drug withdrawal states and depression with regard to phenomenology and neurobiological substrates (e.g., Markou & Kenny, 2002; Markou, Kosten, & Koob, 1998).…”